CO 2 as a sustainable carbon synthon for advanced chemical manufacturing

1 Introduction

1.1 The imperative for CO2 as a sustainable carbon synthon in next-generation manufacturing

Anthropogenic CO₂ emissions, primarily arising from fossil fuel combustion, industrial activities, and land-use change, have driven an unprecedented increase in atmospheric CO₂ concentrations since the Industrial Revolution. According to the National Oceanic and Atmospheric Administration (NOAA), the global average atmospheric CO₂ concentration exceeded 422 ppm in 2024, 426 ppm in 2025 and continues to rise reaching approximately 428 ppm in 2026, reflecting a sustained upward growth trend. Increased atmospheric CO₂ is the principal driver of climate change, contributing to global warming, ocean acidification, sea-level rise, biodiversity loss, and alterations in terrestrial and aquatic ecosystems. Addressing this challenge requires approaches that extend beyond emission mitigation toward integrated carbon utilization pathways capable of supporting resource efficiency, industrial decarbonization, and long-term sustainability (Vega et al., 2024). Global decarbonization strategies envision achieving net-zero emissions with multiple international roadmaps indicating that substantial reductions in greenhouse gas emissions will be required before 2050 to limit global temperature rise (Fam and Fam, 2024). After decades of focusing on lignocellulosic biomass as a renewable feedstock for commodity chemical production (Raheja et al., 2024; Sharma et al., 2024), a paradigm shift is now emerging toward carbon capture and utilization (CCU), which transforms CO₂ from an environmental liability into a valuable carbon resource. CCU has demonstrated potential for mitigating CO₂ emissions by treating CO₂ not merely as a waste stream requiring sequestration, but as a sustainable carbon synthon that can support circular manufacturing and reduce dependence on fossil-derived feedstocks (Kumar et al., 2026). In addition, CCU can support energy storage, carbon recycling, and long-term carbon management across manufacturing, industrial, and transport sectors. For example, CO₂ can be converted into polymers, plastics, or building materials, thereby reducing the reliance on traditional fossil-based feedstocks.

Beyond its role as a greenhouse gas, CO₂ has emerged as a building block or sustainable C1 synthon for the synthesis of value-added chemicals, fuels, and advanced materials. As an abundant, non-toxic, inexpensive, and renewable feedstock, CO₂ can be directly utilized in organic synthesis through carboxylation reactions to produce carboxylic acids, esters, urea, and cyclic carbonates. Furthermore, advances in catalytic C–C and C–N coupling, and CO₂ reduction technologies have enabled the conversion of CO₂ into multi-carbon (C₂+) products, including alcohols, olefins, and oxygenates, thereby expanding its utility as a versatile chemical feedstock (Chakraborty et al., 2025).

Recent years have witnessed a conceptual transition in carbon utilization strategies, moving beyond traditional carbon management approaches toward integrated carbon conversion frameworks. Concepts such as Power-to-X systems, carbon valorization, carbon circularity, and renewable electricity-driven manufacturing have accelerated the emergence of pathways capable of converting captured CO₂ into fuels, chemicals, materials, and other value-added products (Grim et al., 2026). Power to X (PtX) refers to a set of technologies that convert renewable electricity into energy carriers such as hydrogen (Power-to-H₂), synthetic fuels (Power-to-Fuels), methane (Power-to-Gas), and chemicals (Power-to-Chemicals), through electrochemical, thermochemical, or biological processes (What is Power, 2025).

The integration of renewable electricity, green hydrogen, advanced catalysts, engineered biological systems, and hybrid conversion architectures has further expanded the chemical space accessible from CO₂. Such developments have positioned CO₂ not only as a waste stream to be mitigated but as a sustainable carbon feedstock within emerging circular carbon economies.

1.2 Energetic and selectivity challenges in CO₂ activation

Despite these advances, CO₂ conversion remains fundamentally challenging because CO₂ exists as a thermodynamically stable, highly oxidized, and energy-deficient molecule. Unlike conventional fossil feedstocks that inherently possess favorable chemical compositions and substantial energy density for downstream processing, CO₂ conversion requires considerable external energy inputs together with efficient strategies for selective carbon activation (Zhang et al., 2025). Consequently, the viability of carbon utilization technologies depends not only on efficient conversion pathways but also on access to sustainable energy sources capable of supporting economically feasible processes (Basotra et al., 2022). The rapid deployment of renewable energy infrastructure, declining electricity costs, and increasing availability of green hydrogen have significantly improved the feasibility of CO₂ conversion technologies by enabling greater integration between sustainable energy systems and carbon transformation processes (Segovia-Hernández et al., 2025). Beyond its environmental relevance, CO₂ offers several advantages as a carbon feedstock, including widespread availability, compatibility with multiple capture routes, and potential integration with distributed manufacturing systems, thereby supporting circular carbon utilization frameworks. Consequently, carbon utilization is increasingly transitioning beyond commodity-scale applications toward high-value manufacturing, where specialty chemicals, functional materials, pharmaceutical intermediates, and advanced biomaterials offer opportunities for both economic viability and product diversification (Segovia-Hernández et al., 2025). However, challenges associated with selectivity, energy efficiency, process scalability, and economic feasibility continue to restrict large-scale deployment, emphasizing the need for commercially viable carbon conversion systems (Gaur et al., 2025).

1.3 Scope and novelty

Recent studies have examined CO₂ utilization from substantially different disciplinary perspectives, but important fragmentation remains between direct carbon conversion and downstream product manufacturing (Vega et al., 2024). assessed thermal, electrochemical, photochemical, and mineralization routes primarily in terms of catalyst and reactor development, technological readiness, modelling, life-cycle performance, and economic feasibility. Their product analysis was largely centred on methanol, methane, carbon monoxide, synthetic fuels, and mineralized construction materials. (Huo et al., 2023), in contrast, evaluated the global and regional feasibility of supplying CO₂ to a future chemical industry, focusing on feedstock availability, transport, sectoral sourcing, life-cycle impacts, and comparatively mature routes to high-volume chemicals (Lopez et al., 2023). examined chemical-industry defossilization through geographically resolved scenarios based principally on renewable electricity, hydrogen, bio-methanol, biomass, and plastic recycling. These systems-level studies establish the infrastructural and environmental conditions under which CO₂-based manufacturing may become feasible, but they do not critically resolve how CO₂-derived intermediates can be converted into structurally complex and functionally differentiated products (Grim et al., 2026). provide the most comprehensive recent analysis of CO₂-conversion chemistry, encompassing electrolysis, photochemical reduction, non-thermal plasma, microbial electrosynthesis, thermocatalytic hydrogenation, fermentation, reactive carbon capture, and synthetic CO₂-assimilation pathways. The study also compared the energy efficiency, carbon-conversion efficiency, product selectivity, scalability, feedstock logistics, economics, and environmental performance. Therefore, integration of chemical, electrochemical, photochemical, and biological routes alone does not constitute a sufficient distinction for the present review. However, the study restricted their scope to pathways that directly transform CO₂ into products or intermediates and excluded subsequent downstream upgrading, such as syngas and alcohol upgrading. This leaves a conceptual gap between the initial generation of CO₂-derived C₁ or C₂+ intermediates and their subsequent conversion into application-specific specialty molecules, functional materials, and biologically active systems.

The present review addresses this gap by treating CO₂ not only as a substrate for direct reduction or fixation but as a source of transferable carbon synthons that connect primary conversion with downstream chemical and biological manufacturing. The discussion follows the formation and subsequent utilization of intermediates such as CO, formate, methanol, carbonates, carbamates, acetyl-CoA, pyruvate, and other C₂+ building blocks. It critically examines how catalytic C–C and C–N bond construction, carboxylation, polymerization, metabolic rewiring, artificial carbon fixation, and bioelectrochemical coupling expand these intermediates into specialty chemicals, non-natural products, advanced solvents, functional polymers, responsive and self-healing materials, biomaterials, and drug-delivery systems.

2 CO₂ valorization through carbon synthon: Advances, challenges, and perspectives

2.1 Chemical platforms for carbon reprogramming

Catalytic conversion of CO₂ is a transformative approach for closing the carbon loop. It has been well documented that catalysts have an important role to play due to their higher conversion efficiency, as the chemical reaction occurs on their surface (Gaur et al., 2022). Owing to its high thermodynamic stability and chemical inertness, most industrial CO₂ utilization processes rely on advanced catalytic systems for facilitating its efficient conversion through diverse catalytic pathways. Recent advancements highlight different catalytic pathways, such as organocatalysis, electrocatalysis, and photocatalysis which have expanded the scope of CO₂ reduction into C₁ and C₂+ intermediates (Kim and Yang, 2025) where these intermediates further undergo catalytic coupling reactions (e.g., C–N and C–C coupling) to produce a wide range of value-added products, including multi-carbon hydrocarbons, alcohols and nitrogen containing compounds (Figure 1). In particular, carbon-based and metal oxide catalysts (e.g., Cu, Fe, and Co. based systems) enhance CO₂ adsorption, electron transfer, and surface activation by improving selectivity towards multi-carbon products such as olefins, alcohols, and oxygenates (Xia et al., 2025). For example, nanostructured Cu-based catalysts demonstrate Faradaic efficiencies of ∼40–60% toward C₂ products such as ethanol and ethylene due to improved CO intermediate coupling on defect-rich surfaces, highlighting the importance of catalyst surface engineering in directing CO₂ reduction pathways (Han et al., 2024). Indium oxide (In₂O₃) based catalysts demonstrated selectivity for CO₂ hydrogenation to methanol by promoting direct CO₂ activation. In₂O₃ has been further optimized through incorporation into bimetallic systems such as Pd–In/ZrO₂ which synergistically advances hydrogen dissociation, enhances surface reactivity, and stabilizes the reaction intermediates thus presenting a new avenue of heterogeneous catalyst system that brings the CO₂-to-methanol conversion closer to industrial viability (Kim and Yang, 2025). However, changes in the oxidation state of surface metals can create adjacent sites with different electron densities. For example, Cu⁺/Cu⁰ or Co⁰/Co^δ+ pairs can perform complementary roles: one site may activate and bind CO₂, while the neighbouring site stabilizes reaction intermediates and supports subsequent bond formation. In bimetallic catalysts, electron transfer between the two metals, together with lattice strain at the interface, can shift the d-band centre and therefore change how strongly intermediates such as CO and CHO bind to the surface. This binding must be carefully balanced. If it is too weak, intermediates desorb before coupling, if it is too strong, they block active sites and slow the reaction. An optimized electronic structure keeps the intermediates sufficiently stable and close together, thereby lowering the energy barrier for CO–CO, CO–CHO, or CO–CH₃ coupling. Surface defects also play an important role. Step edges, kinks, grain boundaries, and other low-coordination sites contain atoms with unfavourable bonds and higher local reactivity than atoms on flat surfaces. These sites can increase the concentration of adsorbed intermediates and orient them in favourable positions for C–C bond formation. As a result, radical-like species such as CO₂•^-, CHO, and CH₃ are stabilized at the interface and are more likely to undergo cross-coupling rather than desorb or follow competing pathways.

Electrochemical technology enables CO₂ activation through proton–electron transfer reactions at catalytic electrodes by blending electrical and chemical CO₂ conversion technologies. This operates at low temperature and pressure and relies on kinetic processes that are influenced by the selection of electrodes, electrolyte, electrocatalyst, and electrochemical cell configurations (Awogbemi and Desai, 2025). Different electrocatalysts, including Cu, Sn, Ag, and Bi have been explored for selective CO₂ reduction and ensure formation of the desired products such as CO, formate, methane, ethylene, and alcohols. Among these, Cu-based catalysts are effective for producing C₂+ products due to their capability to facilitate C–C coupling pathways, whereas Au and Ag electrocatalysts selectively reduce CO₂ into CO with Faradaic efficiencies exceeding 90%, which can act as an intermediate for the synthesis of formamide through further electrochemical C–N coupling reactions with nitrogen containing co-reactants such as ammonia (Garcia et al., 2025). Moreover, Cu-based electrocatalysts have also been reported to convert CO₂ and N-sources into urea via C–N bond formation achieving Faradaic efficiencies of ∼35–40% (Jia et al., 2024). Electrocatalytic reduction using defect-rich silver (Ag-D) catalyst as key material exhibited ∼100% Faradaic efficiency for the conversion of CO₂ to CO (Table 1) (Garcia et al., 2025). However, the performance of electrocatalysts is hindered by poor selectivity, low activity and stability, and limited robustness. Further research and evaluation are required to advance the application of electrochemical CO₂ reduction. Furthermore, advances in electrochemical reactor designs, such as membrane electrode assembly, gas-diffusion electrodes, and flow-cell systems have upgraded catalytic activity, product selectivity and also facilitate efficient electron, ion, and mass transfer during CO₂ reduction (Garcia et al., 2025).

TABLE 1. Comparative performance, key products, and advantages of representative electrocatalytic, photocatalytic, and biohybrid platforms for CO₂ conversion.

Abbreviation: FE, faradaic efficiency; STC, Solar-to-Chemical; PHB, polyhydroxybutyrate; PV-EC, Photovoltaic-electrochemical systems; GDE, gas diffusion electrode; RHE, reversible hydrogen electrode; COF , covalent organic framework; PSC , patterned perovskite solar cell; Sn-GDE , sn catalysts deposited on a gas diffusion electrode.

Photochemical platform uses renewable solar energy to drive the transformation of CO₂ via semiconducting photocatalysts (Alli et al., 2025). This transformative pathway is governed by five fundamental steps: photoexcitation generates electron-hole (e⁻/h⁺) pairs followed by charge carrier separation to minimize recombination and energy loss, CO₂ adsorption activates the CO₂ for electron transfer, surface redox reactions drive proton-coupled electron transfer to CO₂ reduction with water oxidation and product formation that desorb from catalyst surface to complete catalytic cycle. The selection of the photocatalytic materials, CO₂ concentration, intensity, and reaction conditions significantly affect the process reaction and product formation. Photocatalytic CO₂ reduction requires semiconductor photocatalysts with suitable band-gap energies, typically ranging from 1.8 to 3.2 eV, to enable absorption across the visible-to-ultraviolet region and provide appropriate redox potentials for water oxidation and CO₂ reduction (Kumaravel et al., 2020). The absorption of light by semiconductor materials generates excited electrons that reduce CO₂ into reactive intermediates. Semiconductor materials such as SiC, ZnO, and TiO₂ have been investigated for light-driven CO₂ reduction. Their photocatalytic performance depends on band-gap energy, surface defects, and cocatalyst modification where ZnO and TiO₂ are predominantly responsive to the ultraviolet region of the solar spectrum. For example, granular silicon carbide (α-6H-SiC) has been reported as an effective photocatalyst for CO₂ reduction to methanol under UV irradiation, achieving a methanol concentration of approximately 1.25 mmol/L with a photonic efficiency of ∼1.95% under controlled conditions (Sajeda and Javaid, 2018). Such systems demonstrate the feasibility of utilizing solar energy to convert CO₂ into non-natural products. However, scalability, low efficiency, high photocatalyst cost, and toxicity are the challenges that must be overcome for effective photocatalytic CO₂ conversion.

2.2 Biological platform for carbon utilization

While catalytic, electrochemical, and photochemical techniques have expanded the scope of CO₂ conversion, they are often constrained by high energy requirements, limited product complexity, and catalyst stability. Complementing these approaches, biological systems offer advantages through enzyme specificity, inherent capacity for molecular complexity, and selectivity. Consequently, integrating biological interventions with conventional chemical pathways has emerged as a promising strategy for broadening the chemical space accessible from CO₂. However, the native metabolic role of CO₂ in biology is fundamentally geared toward biomass formation and primary metabolites. Redirecting these systems toward specialty chemicals and advanced materials therefore requires deliberate intervention at the organismal, genetic, and system-integration levels (Li et al., 2024; Mustafa et al., 2026). Beyond classifying organisms solely based on metabolic pathways, the inclusion of carbon utilization modes and culture conditions provides a comparative understanding of the physiological requirements of different biological systems and the operational conditions governing CO₂ assimilation, thereby aiding in the selection of appropriate microbial platforms for sustainable carbon-based biomanufacturing.

2.2.1 Native biological platforms for carbon assimilation

Naturally occurring autotrophic organisms, including cyanobacteria, microalgae, and chemolithoautotrophic bacteria, form the foundational platforms for biological CO₂ conversion and utilization (Daneshvar et al., 2022; Kurt et al., 2023; Sathiyanarayanan and Esteves, 2025). These organisms capture and assimilate CO₂ into central metabolic intermediates through carbon fixation pathways such as the Calvin-Benson-Bassham (CBB) cycle, the Wood–Ljungdahl (WL) pathway, and the 3-hydroxypropionate cycle (Figures 2A–C) to assimilate CO₂ into central metabolites (Manman Li, 2024; Ruan et al., 2025). These pathways convert CO₂ into key carbon synthons such as acetyl-CoA, pyruvate, and glyceraldehyde-3-phosphate, which serve as building blocks for synthesis of value-added products. Microalgae like Chlorella and Nannochloropsis, along with cyanobacteria such as Synechococcus and Synechocystis, assimilate CO₂ from flue-gas or industrial off-gases, producing biomass that can be further valorized into biofuels, animal feed, or chemical feedstocks (Udaypal et al., 2024). Likewise, acetogenic bacteria such as Clostridium, Sporomusa, and Eubacterium species use WL pathway to convert CO₂ plus H₂ (or CO) into acetyl-CoA and acetate, a key carbon synthon for biofuels, and biopolymers (Lee et al., 2022). Laboratory studies confirm that these organisms can thrive on CO₂-H₂ mixtures derived from industrial or electrolysis-based sources, yielding biologically produced acetate at industrially relevant titers (Ammam et al., 2016; Heffernan et al., 2020; Ragsdale and Pierce, 2008; Wood et al., 2023). Similarly, native methanogens such as Methanobacterium and Methanosarcina fix CO₂ into methane which serves an energy carrier while engineered methanotrophs converts methane into methanol and other organic products (Cwicklinski et al., 2024).

Beyond single-organism cultures, native CO₂-fixing strains have been integrated into synthetic microbial consortia to improve assimilation of products (Cestellos-Blanco et al., 2022; Lazaratou et al., 2024). For example, an addition of a small inoculum of the native non-photosynthetic microbial community (NPMC) increased the net CO₂ fixation of synthetic microbial consortia from approximately 3–4–31 mg C/L, representing an approximately 9–10-fold enhancement in the three-member consortium (Hu et al., 2016). Multispecies microbial communities from salt-marsh sediments and wastewater treatment sludge were coupled with iron-based catalysis to hydrogenate CO₂, producing formate, acetate, and butyrate over weeks without pH adjustment, highlighting that native consortia can sustain long-term CO₂ conversion into valuable carboxylates under industrial-like conditions (Blanchet et al., 2018). Enriched mixed microbial cultures convert CO₂ and bicarbonate into volatile fatty acids which were subsequently transformed into polyhydroxybutyrate (PHB), a biodegradable polymer (Bodhe and Gokuladoss, 2026). The suitability of biologically captured CO₂ for valorization is influenced by the carbon source, operating conditions, CO₂ concentration, microbial strain, nutrient supply and formation of key metabolic intermediates. (Pruvost et al., 2022). High CO₂ fixation efficiencies ensure a continuous supply of intracellular carbon intermediates which can be redirected towards synthesis of specialty chemicals, advanced materials, and other value-added products.

However, despite promising laboratory-scale results, the industrial implementation of microalgal CO₂ capture remains restricted by several challenges. Gas–liquid mass-transfer limitation reduces gas-liquid contact and CO₂ availability to microalgal cells due to increase in the reactor size. High gas-flow rates decrease CO₂ utilization by shortening gas residence time and reducing absorption efficiency. Light availability becomes uneven in dense cultures and large-scale systems thereby reducing photosynthetic efficiency and carbon assimilation (Ali et al., 2026). Moreover, large-scale cultivation also requires substantial land area and photobioreactor volume for CO₂ sequestration resulting in high capital cost, and greater energy demands. These constraints explain why laboratory-scale systems, which benefit from uniform light exposure and controlled conditions, often report higher carbon utilization efficiency than large-scale operations.

2.2.2 Synthetic biology and engineering-driven carbon approaches

Engineering artificial autotrophy in model heterotrophs represents a foundational breakthrough, as it enables the direct coupling of CO₂ fixation with highly versatile synthetic metabolic networks traditionally optimized for non-natural product synthesis (Yu et al., 2022). This shift marks a transition from natural carbon assimilation toward programmable carbon utilization systems, where metabolic pathways are rewired to channel fixed CO₂ into central carbon synthons such as acetyl-CoA, pyruvate, phosphoenolpyruvate, and glyceraldehyde-3-phosphate, thereby enabling the biosynthesis of specialty chemicals, fuels, polymers, and pharmaceutical precursors. Reported studies, listed in Table 2 has demonstrated success in engineering bacteria and other organisms to assimilate CO₂ efficiently, often beyond natural limitations (Onyeaka and Ekwebelem, 2023; Tommasi, 2024). These efforts leverage synthetic biology tools such as CRISPR-Cas for precise genome editing, pathway optimization, and co-culture strategies allowing control over carbon partitioning and metabolic flux (Raheja et al., 2022; Singh et al., 2023) (Figure 3A). A notable breakthrough is the conversion of traditionally heterotrophic systems such as Escherichia coli into artificial autotrophs by introducing CO₂ fixation pathways coupled with adaptive laboratory evolution (Flamholz et al., 2020). This achievement effectively enables the use of CO₂ as a primary carbon source within one of the most widely utilized industrial microbial chassis, thereby expanding its utility toward sustainable chemical production. In parallel, industrially relevant yeasts such as Saccharomyces cerevisiae and Pichia pastoris have been engineered to assimilate CO₂, either through the introduction of fixation pathways or by recycling CO₂ generated during metabolism (Gassler et al., 2020; Li et al., 2017; Xia et al., 2017; Zhong et al., 2026). This effectively moves toward closed-carbon fermentation systems capable of producing complex molecules such as terpenoids and other intermediates (Yu et al., 2025).

TABLE 2. Biological interventions for carbon dioxide (CO₂) utilization as a feedstock for non-natural and novel products, summarizing native organisms, engineered systems, and bio-electrochemical platforms.

The native autotrophs such as cyanobacteria have been extensively modified through the incorporation of heterologous pathways to produce non-native compounds including 1-butanol, lactate, and other reduced chemicals (Liu et al., 2019; Shabestary et al., 2021; Yunus et al., 2022). This metabolic redirection highlights the feasibility of diverting photosynthetically fixed carbon away from growth-associated pathways toward energy-dense and industrially relevant products. Beyond photosynthetic systems, engineered Clostridium species and co-cultures to convert CO₂ into sustainable fuels, packaging materials, and platform chemicals like acetone and isopropanol, non-native outputs not produced by wild strains, using the WL pathway enhanced by gene overexpression and metabolic flux redirection (Bachleitner et al., 2023; Liew et al., 2022), with successful demonstration at pilot-scale reactors, underscoring their industrial relevance. In 2024 a detailed review study reveals the microbial CO₂ fixation advancements, identifying efficient enzymes and pathways for biofuels and high-value bioproducts (Li et al., 2024), emphasizing cell factory designs in acetogens and cyanobacteria that integrate CO₂ into central metabolism for yields up to 50% higher than natural systems. The emergence of CRISPR–Cas-based genome editing (Liu et al., 2019), has further accelerated these developments by enabling precise control over metabolic flux, gene expression, and pathway integration across diverse CO₂-utilizing organisms. CRISPR-enabled reprogramming of CO₂-metabolizing microbes, has enabled cyanobacteria and methanogens to produce ethanol and other fuels directly from CO₂, addressing electron supply challenges through hybrid electro-biological systems (Yu et al., 2022). Membrane electrode assembly (MEA) regulate the CO₂ concentration and pH at the electrode–microbe interface, thereby facilitating efficient electron transfer and enhancing microbial CO₂ fixation. This engineering strategy mimics the carbon-concentrating mechanism (CCM) of photosynthetic microorganisms, which increase CO₂ availability around the carbon-fixing machinery to improve assimilation efficiency. For instance, modified Rhodopseudomonas palustris to generate carbon-neutral biofuels using only CO₂, light, and solar-generated electricity, a process now scaled in mixotrophic fermentations (Bai et al., 2021). These developments collectively demonstrate how CRISPR-based regulation serves as a central control layer for optimizing carbon flux in engineered phototrophic and chemolithotrophic systems. Recent applications of CRISPR–Cas systems in microalgae provide clear evidence of how precise genome editing can enhance CO₂ fixation while simultaneously enabling the production of high-value biomolecules. For example, targeted knockout of the CIA5 gene in Chlamydomonas reinhardtii, a key regulator of the carbon-concentrating mechanism, significantly improved growth under elevated CO₂ conditions and achieved CO₂ removal efficiencies exceeding 20% (Asadian et al., 2022). Similarly, disruption of metabolic genes such as phospholipase A2, ADP-glucose pyrophosphorylase (AGP), and zeaxanthin epoxidase (ZEP) led to enhanced accumulation of lipids, lutein, and zeaxanthin, demonstrating effective redirection of fixed carbon toward industrially relevant products (Shin et al., 2019; Song et al., 2022).

Despite significant progress has been made in synthetic biology and metabolic engineering, the biological conversion of CO₂ into high-value products is still affected by several inherent metabolic limitations (Mustafa et al., 2026). Most fixed carbon is diverted to storage and growth-related pathways such as biomass, glycogen, starch, and lipids rather than to target products. Furthermore, CO₂ reduction requires high requirements for ATP, NADPH/reduced ferredoxin, and efficient electron transfer (Zhao et al., 2026). The limited catalytic capacity of key enzymes such as RuBisCO and feedback inhibition posed by intermediates (such as pyruvate and acetyl-CoA) limits carbon flux to target products (Mengyao Li et al., 2020; Wang et al., 2022). To overcome these constraints, modern metabolic engineering strategies focus on dynamic control of carbon flux (Zhao et al., 2026). Push–pull metabolic engineering (enhances precursor availability and minimize the feedback inhibition), CRISPRi-based gene control (programmable transcriptional control), metabolite-sensitive regulatory mechanisms, and synthetic genetic circuits and kill-switches redirect carbon away from growth-related pathways and toward desired fuels, specialty chemicals, and biopolymers (Liang et al., 2026; Mustafa et al., 2026). Hence, integration of enzyme engineering, synthetic biology, adaptive laboratory evolution, and systems metabolic engineering play a key role in mitigating these biological limitations to increase CO₂ utilization efficiency, productivity, and industrial viability.

2.2.3 Bioelectrochemical interfaces for carbon valorization

Bio-electrochemical systems (BES) represent an emerging and promising platform for the utilization of CO₂ as a carbon feedstock, enabling its conversion into non-natural or novel products through the integration of microbial catalysis with an external electrical input (Figure 3B) (Awogbemi and Desai, 2025). In these systems, electroactive microorganisms located at the cathode can acquire electrons either directly or indirectly via redox mediators and subsequently use them to drive CO₂ reduction into a range of value-added compounds. The nature and specificity of the products formed are largely determined by the metabolic capacity of the microbial strain and the extent of pathway engineering applied. Recent advances in BES have been closely linked to improvements in electrode architecture, microbial catalyst performance, process optimization, and the integration of hybrid systems with separation technologies or complementary electrochemical processes (Corona-Martínez et al., 2025). Several studies have demonstrated the practical potential of BES for CO₂ bioconversion. For instance, BES have been utilized for the biotransformation of CO₂ into quality biomethane and acetic acid (Roy et al., 2021), leveraging the effectiveness of Acetobacterium spp. And biocathodes. This highlights the role of hydrogenotrophic and acetogenic microorganisms in carbon capture and product formation. Likewise, the bioconversion of CO₂ into acetate, butyrate, isovalerate, and caproate through effective deployment of novel microbial electrosynthesis (MES) was further demonstrated and the high conversion efficiency was traced to the effectiveness of the electrocatalysts (Izadi et al., 2021). These findings indicate that BES can be tailored not only for carbon recycling, but also for the synthesis of a broad spectrum of carboxylates and related chemicals. More recently, research attention has shifted toward improving reactor design, electrode composition, separator materials, and the selection of electroactive microorganisms in order to enhance electron transfer and product selectivity (Quraishi et al., 2021). This system-level optimization is increasingly important because the effectiveness of BES depends on the coordinated performance of biological, chemical, and engineering components. Although, it has been noted that MES mixed cultures mostly give low-value products, while engineered pure cultures could enable higher-value electrobioproduction (Harnisch et al., 2024). Collectively, these studies suggest that BES technology is evolving from a concept focused mainly on carbon utilization into a technologically sophisticated platform for the sustainable production of fuels, chemicals, and novel bioproducts.

Successfully moving biological and hybrid CO₂ utilization technologies from laboratory research to commercial scale will require coordinated advances in metabolic engineering, reactor design, and process integration (Mustafa et al., 2026). Efforts over the next 5 years should focus on improving carbon fixation efficiency, intracellular carbon flux regulation, and electron transfer through advanced synthetic biology, with targeted carbon utilization efficiencies exceeding 70%–80% and continuous biocatalytic operation for >1,000 h (Liang et al., 2026; Taha et al., 2025). Within the next 10 years, the focus should be on pilot-scale hybrid bioelectrochemical systems that integrate renewable electrical energy, automated process control, and continuous bioprocessing to achieve high space–time yields, faradaic efficiency (>95%) (Alli et al., 2025), and long-term reactor stability. Over the next 20 years, commercial viability will depend on achieving low-cost renewable electricity (Levelized Cost of Energy, LCOE < US$40–60 MWh^-1) (Bamisile et al., 2025), biocatalyst lifetimes exceeding 1–2 years, high carbon conversion efficiencies (>85%) (O’Brien et al., 2021), and economically competitive production costs. Achieving these milestones will enable hybrid bioelectrochemical platforms to move beyond proof-of-concept laboratory systems into large-scale, deployable and economically viable technologies that enable sustainable carbon biomanufacturing.

3 CO₂ as a renewable carbon synthon for high-value manufacturing

3.1 Specialty chemicals and functional molecular intermediates

CO₂ has emerged as an attractive C1 carboxylation agent for the sustainable synthesis of carboxylic acids, offering one of the most atom-efficient routes for CO₂ utilization. One of the most atom-efficient strategies for CO₂ utilization is direct carboxylation, in which CO₂ acts as a C1 synthon for the formation of carboxylic acids (Sable et al., 2021). The classical Kolbe–Schmitt reaction is mostly limited to phenolic substrates and needs high temperatures and pressures. However, modern catalytic methods have greatly expanded the range of substrates that can be used. Recent improvements in homogeneous and heterogeneous catalysis have made it possible to carboxylate aromatic hydrocarbons, heteroarenes, and highly functionalized substrates under relatively mild conditions. This opens up new chemical spaces that CO₂ can reach (Chen et al., 2025; Gooßen et al., 2008). Transition-metal-catalyzed carboxylation has been a crucial component of this development. Nickel, copper, palladium, and rhodium complexes have been shown to contribute to CO₂ efficiently add to a wide range of organometallic and organohalide precursors (Saini et al., 2022; Tortajada et al., 2018). These include aryl halides, organoboranes, organozincs, and, more recently, inactivated C-H bonds. These methods make it feasible to get structurally different benzoic acid derivatives, heteroaromatic carboxylic acids, and polyfunctional intermediates. They also tend to be more selective and tolerant of functional groups than traditional fossil-based methods (Pichette Drapeau and Gooßen, 2016; Tortajada et al., 2018). The carboxylation of heterocycles with CO₂ is critical because heteroaromatic motifs like pyridines, indoles, thiophenes, furans, and imidazoles are very prevalent in pharmaceuticals and agrochemicals. In this context, electrochemical and photocatalytic carboxylation methods have become more popular as ways to work with thermochemical catalysis (Sun et al., 2024; Zhang et al., 2020). These methods make it possible to activate CO₂ and make C–C bonds at low temperatures and pressures, often at room temperature and pressure, while reducing or eliminating the need for stoichiometric organometallic reagents (Pichette Drapeau and Gooßen, 2016; Sun et al., 2024). As a result, they offer improved selectivity, and sustainability with sensitive functional groups.

From a mechanistic perspective, the primary pathway in the majority of catalytic systems involves the incorporation of CO₂ into a metal-carbon bond, generally subsequent to oxidative addition or transmetalation steps (Braunstein et al., 1988). However, there are currently growing numbers of reports of direct C-H activation followed by carboxylation (Pichette Drapeau and Gooßen, 2016; Tortajada et al., 2018). This is a big step towards processes that use fewer steps and create less waste. Importantly, life cycle assessments indicate that when these carboxylation reactions are powered by renewable electricity or coupled with green hydrogen, CO₂-derived carboxylated aromatics can exhibit substantially lower greenhouse gas emissions than their petrochemical counterparts (Styring et al., 2015). This advantage is particularly pronounced at small-to-medium production scales, which are characteristic of the specialty chemicals sector, reinforcing the role of CO₂ carboxylation as a viable and sustainable platform for next-generation chemical manufacturing. Chemical CO₂ capture generates several reactive carbon-containing species that can serve as intermediates for subsequent utilization. In aqueous amine systems, primary and secondary amines predominantly capture CO₂ through carbamate formation, whereas tertiary and sterically hindered amines favor bicarbonate formation. Although carbamate formation enables rapid CO₂ absorption, its relatively strong binding generally increases the energy required for solvent regeneration (Chai et al., 2022). In contrast, bicarbonate-rich systems can facilitate easier regeneration and may be more compatible with integrated mineralization and utilization pathways. Alkaline absorbents such as NaOH and KOH capture CO₂ as bicarbonate and carbonate species. For example, NaOH reacts with CO₂ to form Na₂CO₃, which can subsequently be converted to CaCO₃ while regenerating the alkaline absorbent (Custelcean, 2022). These capture-derived carbamate, bicarbonate, and carbonate species therefore represent not only intermediates in CO₂ separation but also potentially reactive carbon pools for integrated capture-and-utilization processes. Their practical utility, however, depends on binding strength, regeneration requirements, downstream reactivity, catalyst compatibility, product separation, and the overall energy demand of the process. Owing to limitations associated with conventional aqueous amine systems, including volatility, corrosion, solvent degradation, and high regeneration-energy requirements, considerable attention has shifted toward advanced capture media for integrated CO₂ capture and utilization. These include ionic liquids (ILs), deep eutectic solvents (DESs), switchable solvents, non-aqueous amine systems, and CO₂-reactive organic liquids, which offer tunable physicochemical properties and potentially lower solvent losses and regeneration requirements (Nwabueze et al., 2024; Zhang et al., 2022). Recent literature indicates a paradigm shift from water-rich, first-generation amine solvents to CO₂-derived and CO₂-enabled advanced solvents, including ionic liquids (ILs), deep eutectic solvents (DESs), switchable solvents, non-aqueous amine systems, and CO₂-reactive organic liquids. These solvents together provide tunable physicochemical properties and enhanced process efficiency (Castro et al., 2025; Chen et al., 2025). Ionic liquids, especially those with amine-functionalized cations or CO₂-philic anions, have very low vapor pressure, are very stable at high temperatures, and dissolve CO₂ very well. Therefore, less solvent is lost, and less energy is needed to regenerate them. However, they are not used as much because they are very thick, expensive to make, and may be toxic (Castro et al., 2025; Fourie et al., 2025). CO₂-derived solvents like dimethyl carbonate (DMC) are examples of how carbon dioxide capture and utilization can work together. They are both green solvents and value-added products made directly from CO₂ and methanol (Son et al., 2025). DMC is well-known for being low in toxicity, biodegradable, having a high dielectric constant, and being useful as a battery electrolyte solvent, fuel additive, and phosgene substitute. However, thermodynamic limits still make it hard to get high yields from direct synthesis, which drives innovation in catalyst and membrane-assisted reactor design (Raza et al., 2022). Importantly, recent perspectives emphasize that the future of advanced CO₂-derived solvents lies in integrated capture–conversion systems, where solvents are designed not only to absorb CO₂ efficiently but also to activate it chemically for downstream conversion or mineralization, thereby reducing overall process cost and enabling new reaction pathways inaccessible to conventional systems (Heldebrant et al., 2022). The literature collectively emphasizes that advanced solvents derived from or facilitated by CO₂-via molecular tunability, diminished environmental impact, and alignment with integrated CCUS strategies constitute a pivotal technological lever for attaining scalable, energy-efficient, and economically feasible carbon management. However, challenges pertaining to viscosity control, long-term stability, and extensive deployment persist as essential domains for continued investigation (Castro et al., 2025; Chen et al., 2025).

Beyond liquid-phase absorption, recent CCU strategies increasingly integrate CO₂ capture and catalytic conversion within multifunctional porous materials. Metal–organic frameworks (MOFs), porous organic polymers, and ionic porous networks can concentrate CO₂ through reversible adsorption while simultaneously providing Lewis-acidic, basic, or ionic catalytic sites for its subsequent transformation (Z. W. Liu and Han, 2019). In MOFs, coordinatively unsaturated metal centers provide Lewis-acidic adsorption sites for CO₂, while amine or heteroatom-functionalized pores enhance affinity through acid–base and electrostatic interactions associated with the quadrupolar nature of CO₂. These interactions improve low-pressure capture but must remain sufficiently reversible to avoid excessive regeneration energy and loss of catalytic accessibility. Moisture and flue-gas impurities can further compete for active sites or destabilize the framework, making adsorption strength, hydrolytic stability and recyclability critical design parameters for integrated capture–conversion systems. Ionic porous organic polymers provide a representative example in which captured CO₂ can be directly converted into organic carbonates (Trickett et al., 2017). Imidazolium-containing porous frameworks combine CO₂-philic ionic sites with nucleophilic counterions that catalyse the cycloaddition of CO₂ to epoxides. Mechanistically, nucleophilic attack opens the epoxide ring to generate an alkoxide intermediate, followed by CO₂ insertion to form an alkylcarbonate species and subsequent intramolecular ring closure to yield the corresponding five-membered cyclic carbonate. The efficiency of this process is therefore governed not only by CO₂ uptake but also by counterion nucleophilicity, accessibility of catalytic sites, pore architecture and stabilization of reaction intermediates. Although high cyclic-carbonate yields have been demonstrated, elevated temperature and CO₂ pressure is still frequently required, highlighting the need to improve catalytic activity under milder conditions. Captured CO₂ can also enter established chemical value chains through sequential reduction and C–C bond-forming reactions (Sani et al., 2022). Hydrogenation of CO₂ with renewable H₂ produces methanol, which can subsequently undergo methanol-to-olefin and methanol-to-aromatic transformations to generate ethylene, propylene, benzene, toluene and xylenes. These routes demonstrate that CO₂ valorization is not restricted to C₁ products but can extend to higher-carbon commodity chemicals through dehydration, oligomerization, cyclization and aromatization reactions. However, their environmental advantage is highly dependent on the origin of H₂ and process energy, because electrolysis and CO₂ capture remains major contributors to the overall energy demand (Rosental et al., 2020).

3.2 Engineering high-performance materials from carbon feedstocks

CO₂ is a sustainable feedstock for developing high-performance functional polymers due to its abundance, low toxicity, nonflammability, and unique structural and lifecycle attributes when incorporated into polymer backbones (Table 3). CO₂ incorporation creates carbonate, ester, and carbonyl linkages, allowing for fine control of thermal, mechanical, dielectric, and degrading properties, making these materials viable alternatives to petroleum-derived polymers (Y. Liu and Lu, 2023). CO₂/epoxide copolymerization is a well-established method for synthesizing aliphatic polycarbonates with controlled molecular weight, stereochemistry, and backbone regularity. This method produces materials suitable for foams, elastomers, and engineering plastics, but challenges like ether defects and limited monomer scope persist (Y. Liu and Lu, 2023). Advances in backbone-editable polymers, synthesized by ring-opening copolymerization of CO₂ with functional epoxides or anhydrides, allow for post-polymerization skeletal rearrangements to adjust glass transition temperature, degradation kinetics, and chemical reactivity without changing molecular weight, enabling unprecedented lifecycle tunability (Niu et al., 2025). Indirect methods convert CO₂ into lactones, which undergo ring-opening polymerisation to create degradable, recyclable polyesters with high CO₂ content and functional handles for post-modification, expanding structural diversity beyond epoxide chemistry (Chen et al., 2024). Hyper crosslinked polymers and organic polymers with CO₂-active motifs have high surface areas, tunable porosity, and strong CO₂ affinity, optimizing gas capture and catalytic conversion while maintaining chemical stability and backbone rigidity (Ullah et al., 2025; Wang L. et al., 2025). CO₂-responsive polymer networks use reversible interactions between CO₂ and basic functional groups to create switchable gels, adaptive membranes, and flow-control materials without chemical degradation (Ullah et al., 2025). Covalent adaptable networks with CO₂-responsive ionic clusters enable rapid recycling under mild conditions, overcoming the trade-off between service temperature and recyclability in high-performance polymers (Chen et al., 2024). Functional polymers with CO₂-tunable backbones are used in electrochemical and energy applications as electrolytes, electrode modifiers, and conductive scaffolds. Their backbone chemistry and pendant functionalities regulate ion transport, stabilize reaction intermediates, suppress hydrogen evolution, and control CO₂ reduction selectivity and syngas composition. Molecular-level backbone design is crucial (Feric et al., 2023; Gao et al., 2025). The literature suggests that rational engineering of CO₂-incorporated polymer backbones, including catalytic control, functional group placement, porosity modulation, and dynamic bond design, can create high-performance, recyclable, and circular economy-aligned materials. However, challenges remain, such as catalyst cost, scalability, and monomer utilization (Liu and Lu, 2023).

TABLE 3. Summary of self-healing mechanisms in CO₂-Derived advanced polymers.

In addition to commodity polymers, materials made from CO₂ are being designed more and more to have advanced functions. Functional polymers that have carbonate, carbamate, or urethane linkages are more durable, resistant to chemicals, and work better with post-functionalization strategies (Yadav et al., 2019). These characteristics have made it possible for them to be used in smart coatings, membranes, and specialty resins, where performance needs go beyond structural integrity to include responsiveness and long life (Beyrami et al., 2025). For example, CO₂-based polymer networks have been used in self-healing materials, where dynamic covalent bonds or reversible intermolecular interactions let micro-scale damage repair itself. These kinds of systems make materials last much longer and need less maintenance, which is good for both the economy and the environment (Lv et al., 2025; Mah et al., 2025). In the context of smart coatings, the utility of CO₂-derived polymers extends beyond passive physical barriers. Because functional polymers containing carbonate or urethane linkages are highly amenable to post-functionalization strategies, active responsive sites can be introduced to meet performance needs that go far beyond basic structural integrity (Yadav et al., 2019). Smart coatings are designed to respond autonomously to local environmental changes, such as shifts in pH, temperature variations, or mechanical stress. For instance, mechanical damage to an anti-corrosion coating can trigger a localized structural rearrangement that seals the breach, preventing the ingress of moisture and oxidative species (Beyrami et al., 2025). Certain CO₂-based polyurethanes exhibit shape-memory properties, where the coating can recover its original topography after deformation upon the application of a thermal stimulus. This is highly valuable in applications where scratch resistance and aesthetic longevity are paramount. Building upon the foundational shift from commodity polymers to advanced functional materials derived from CO₂, the literature highlights a critical intersection of synthetic chemistry, material longevity, and sustainability (Yadav et al., 2019). The transition of CO₂-based polymers (such as polycarbonates and non-isocyanate polyurethanes) into the realm of self-healing materials relies heavily on the incorporation of reversible chemistries. Unlike traditional cross-linked thermosets, which suffer permanent failure upon yielding, these advanced networks utilize intrinsic repair mechanisms that allow micro-scale damage to repair itself, significantly extending the material’s lifespan (Lv et al., 2025; Mah et al., 2025). NIPUs can be used as a sustainable alternative to conventional polyurethanes as they are synthesized from cyclic carbonates and diamines without isocyanate or phosgene-derived intermediates. NIPU offers increased chemical resistance, lower permeability, improved water absorption, and thermal stability thereby reducing energy requirements. NIPU also have the potential to lower fossil resource dependence and greenhouse gas emissions compared with conventional polyurethane production highlighting the importance of holistic life-cycle assessment when evaluating their contribution to net-zero objectives (Turnaturi et al., 2023).

Researchers are increasingly embedding dynamic covalent linkages such as Diels–Alder adducts, disulfide bonds, and dynamic imine or boronic ester bonds into the polymer backbone. Under specific stimuli (like mild heat or UV light), these bonds can temporarily dissociate and re-form across microscopic fracture interfaces, effectively closing micro-cracks before they propagate into macroscopic failures (Lv et al., 2025). Alongside covalent strategies, reversible non-covalent interactions offer a distinct healing pathway. Heavy utilization of dense hydrogen-bonding arrays, metal-ligand coordination, and ionic interactions allows these carbonate and urethane networks to achieve autonomous healing, even under challenging environmental conditions like high humidity (Mah et al., 2025).

3.3 Can carbon emissions become biomedical resources?

The CO₂-derived platform chemicals discussed in Section 2 including CO, methanol, formate, and C₂+ intermediates, serve as versatile carbon building blocks for downstream chemical and biological transformations. Through catalytic and microbial mechanism, these intermediates can be converted into high-value biomolecules, pharmaceuticals, and functional biomaterials, thereby linking carbon valorization with life-science applications.

3.3.1 CO₂-derived biocompatible polymers and functional biomaterials

Global plastic production has reached 360 million tons in 2020, intensifying environmental and health concerns underscoring the urgent need for sustainable alternatives to conventional synthetic plastics (Gaur et al., 2025a; Gaur et al., 2025b). Bioplastics made from renewable and biodegradable resources offer promising solutions towards eco-friendly, biodegradable and non-toxic materials. In this context, CO₂ has emerged as a valuable C1 feedstock for the synthesis of aliphatic polymers, particularly polycarbonates (PCs). The copolymerization of CO₂ with epoxides or transesterification of dimethyl carbonate with diols produces polyalkylene carbonates which serve as a key intermediate for the synthesis of polyurethanes (PUs) and other functional polymers. Additionally, the reaction of CO₂ with formic acid, propylene oxide or cyclohexane oxide enables the formation of high-molecular weight polyoxymethylene, polypropylene carbonate (PPC) and poly-cyclohexenecarbonate (PCHC) enhancing the advantage of CO₂ based polymers (Florjańczyk et al., 2022; Saleem et al., 2023). These CO₂ based polyols can reduce greenhouse gas emissions by 11%–19% and save fossil resources by 13%–16%. Recent studies have reported the successful conversion of CO₂ into polymeric materials (Chen Liu et al., 2024). reported the copolymerization of CO₂ with 1,2-butylene oxide to synthesize polycarbonate-ether polyols using a Zinc-Cobalt (Zn–Co) layered double metal cyanide catalyst, displaying high catalytic activity (productivity up to 1500 g polymer/g catalyst) and a CO₂ incorporation rate of 35.5%. Similarly, researchers synthesized bio-based polycarbonates via copolymerization of glycidyl four-pentenoate (GPA) with CO₂ using a Bis(triphenylphosphoranylidene)ammonium Chloride (SalenCoCl/PPNCl) catalyst, resulting in polymers with enhanced structural performance including improved mechanical strength, higher thermal stability and increased functionalization potential (Wang et al., 2023). Building on such advances in CO₂ based polymer synthesis, studies have further explored versatility of catalytic system by developing triblock copolymers, poly (cyclohexene carbonate-b-ε-decalactone-b-cyclohexene carbonate), using a switchable Zn(II)/Mg(II) catalyst system. This approach addressed the inherent brittleness and low elongation at break of conventional CO₂ derived PCHC homopolymers. The resulting triblock copolymers exhibited improved thermal and mechanical performance including high elongation at break (>900%), significant toughness (∼112 MJ/m), and good thermal stability, with a Td,5 (temperature at 5% weight loss) of approximately 280 °C while maintaining 6–23 wt% CO₂ incorporation, ∼99% selectivity, and >90% monomer conversion (Sulley et al., 2020). Further, CO₂-derived polycarbonates broaden the application by offering potential for use in the biomedical field due to their inherent biocompatibility. For instance, metal-free TEB/PPNCl-catalyzed terpolymerization of CO₂ and propylene oxide yields benzophenone-functionalized polycarbonates (PPCB) with significantly improved UV stability and strong antimicrobial activity. Their functionality can be modified with benzophenone tetracarboxylic dianhydride that demonstrated strong antibacterial activity, achieving bacteriostatic efficiencies of 99% and 91% against Staphylococcus aureus and E. coli respectively (Huang et al., 2023). These results highlight the potential of CO₂-based biocompatible polymers in designing antibacterial and bacteriostatic surfaces for biomedical devices and biomaterial applications.

3.3.2 Carbon-based building blocks for advanced drug delivery

Leveraging biocompatibility and physicochemical properties of CO₂ derived polymers, research has explored their application in advanced drug delivery systems (Figure 4). Polycarbonates made by copolymerizing CO₂ with epoxides can have a high molecular weight and contain both hydrophilic and hydrophobic domains. Because of this, they can form micelles, nanoparticles and hydrogels, which are useful for targeted drug delivery. Harnessing these advantages, studies have reported that CO₂-based polycarbonates nanoparticles encapsulating anticancer drug such as doxorubicin, demonstrated enhanced cellular uptake and reduced systemic toxicity compared to conventional delivery systems (Yu et al., 2021). For instance, a CO₂-responsive supramolecular drug carrier system was developed by combination of hydrophobic imidazole-containing rhodamine 6G (I–R6G) anticancer agent with hydrophilic ureido-cytosine (UrCy) end-capped polyethylene glycol (UrCy-PEG). The resulting self-assembled nanocarrier potentially enhances effectiveness of cancer treatment (Ngan et al., 2023). Likewise, CO₂-derived polycarbonate-polypeptide nanocarriers have shown profiles for tumor-targeted therapy. This enabled the integration of targeting ligand to achieve receptor specific drug delivery. For example, researchers engineered epidermal growth factor receptor (EGFR)-targeted gemcitabine (GEM)-conjugated polymeric mixed micelles (GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC) to treat pancreatic cancer. The incorporation of the GE11 peptide, a ligand with high affinity for EGFR, enriched the micelles with tumor-targeting potential, enabling superior binding and uptake by EGFR-overexpressing pancreatic tumor cells. In vitro, GE11-functionalized micelles exhibited significantly improved cellular internalization in EGFR-positive cancer cells compared to non-targeted carriers. In mouse models of pancreatic cancer, these targeted micelles attained considerable tumor accumulation and resulted in clear inhibition of tumor growth, underlining the therapeutic benefit of combining receptor-mediated targeting with CO₂-based polycarbonate drug-conjugated nanocarriers (Li Wang et al., 2024).

3.3.3 Pharmaceutical intermediates through carbon fixation chemistry

Carboxylic acids and their derivatives, designed through the carboxylation of carbon nucleophiles using CO₂, correspond to key structural motifs in pharmaceuticals and other materials. Among carboxylation strategies, C–H bond carboxylation with CO₂ has gained attention due to its efficient use of reactant atoms and ability for carbon consumption. The Kolbe–Schmitt reaction, first reported in the 1860s, remains a basis in industrial chemistry for the ortho-carboxylation of phenoxides with CO₂, allowing the synthesis of salicylic acid, the precursor to Aspirin (Luo and Larrosa, 2017). Hydroxyaromatic carboxylic acids (HACAs), including hydroxybenzoic acid, salicylic acid and hydroxynaphthoic acid and its derivatives are essential feedstocks within pharmaceutical and other related industries. Currently, large-scale HACA production exploits petroleum-derived phenolics, operating conditions at ∼125 °C and ∼85 bar to achieve high conversions (∼99%). However, because this process consumes CO₂ directly, it holds inherent potential for contributing to industrial CO₂ sequestration and contributes to net zero (Mohammad et al., 2023). Recent advances further demonstrate that bio-derived phenolic substrates can undergo Kolbe–Schmitt carboxylation to yield high-value hydroxybenzoic acids. Notably, carboxylation of mixed biomass-derived phenolic salts under 175 °C–225 °C and 30 bar CO₂ enhanced dicarboxylic acid formation, producing up to 41.9% 2,3-dihydroxyterephthalic acid and 20.5% 2-hydroxyisophthalic acid, with syringic acid yields increasing from <2% to ∼33% in mixed systems (Mohammad et al., 2025). These di-carboxylated products are valuable intermediates for pharmaceutical API synthesis, highlighting the advantages of both feedstock valorization and CO₂ utilization in chemical manufacturing. Catalyst design and productivity remain major challenges. Many catalytic systems developed for CO₂-epoxide copolymerization or CO₂-based carboxylation demand costly metals, show restricted substrate scope, or demand high temperatures and pressures. Similarly, while CO₂-derived polycarbonates and polycarbonate-ether polyols exhibit promising biocompatibility and mechanical properties, their long-term stability, low reaction rates, degradation behavior, and regulatory acceptance in biomedical environments necessitate further consideration. For pharmaceuticals, although Kolbe–Schmitt carboxylation is well-developed, the direct C–H carboxylation approaches using CO₂ are still restricted in selectivity, functional group tolerance, and scalability, limiting the diversity of APIs and intermediates that can be synthesized using CO₂ as a feedstock.

4 Challenges, opportunities, and future directions

Despite the considerable promise of CO₂ capture and utilization technologies, several challenges persist including technological limitations, high energy requirements and economic feasibility (Beniwal et al., 2025). Addressing these challenges is essential for revealing full potential of CO₂ transformation and therefore paving the way towards sustainable industrial growth. The catalytic process of thermochemical conversion of CO₂ has been well-explored. However, challenges such as low conversion rate and catalyst instability often causes hindrance in commercialization. For example, Ni and Cu-based catalyst for CO₂ hydrogenation to methanol synthesis are constrained by the high thermodynamic stability and kinetic inertness of CO₂ which necessitates efficient catalyst-mediated activation. Ni-based catalysts promote methanation and the reverse water–gas shift (RWGS) reaction, thereby reducing methanol selectivity, whereas Cu-based catalysts, despite being highly active for methanol synthesis, are susceptible to sintering and deactivation under prolonged operating conditions (Yadav et al., 2024). Emphasis on the design of robust, inexpensive catalysts capable of operating under milder conditions can lead to process intensification in near future. The electrochemical CO₂ reduction is still confined to laboratory scale. The major limitations of electrochemical reduction include low solubility of CO₂ in aqueous electrolyte and its random distribution on the electrode interface causing reduction in efficiency and hindrance in the scalability of the process (Belsa et al., 2024). On the other hand, photochemical technique is also not commercialized yet. Current photoelectrochemical cells have been reported to exhibit an efficiency of below 10%. Further, the reaction mechanism and stability issues are also not fully explored. Future research must focus on increasing the stability and efficiency of photoelectrochemical cells. Further, improving reactor design along with regeneration of photocatalyst will pave the way towards sustainability. CO₂ conversion via biological routes offers several advantages but maintaining high cell densities with stable growth conditions in reactors is often challenging (Suman Bajracharya, 2017). Apart from that, product selectivity and specificity have always been a major hurdle, complicating the downstream process. The instability of enzymes and microbial strains at industrial scale requires recurrent replacements and thereby raising costs. Efforts must focus on developing more resilient strains and utilizing existing industrial infrastructure for the developed bioconversion systems. Across all conversion methods, efficiency, controlling product selectivity and cost-effectiveness are central challenges. In addition, assessing CO₂ conversion only through selectivity or Faradaic efficiency may overestimate its sustainability (Zhang et al., 2025). The energy required for product concentration and purification must also be considered, particularly for dilute aqueous bioproducts. In CO₂ fermentation to acetic acid, a broth containing only 1.5 wt% acetic acid required filtration, ion exchange, liquid–liquid extraction, and azeotropic distillation to achieve 99.9 wt% purity, resulting in a downstream utility demand of 124.57 MJ/kg product. Although heat integration substantially reduced utility consumption, the study demonstrates that low product titres can impose a major separation burden (Regis et al., 2025). Overcoming these challenges needs holistic approaches that integrate the development of advanced catalysts with modified reactor designs such as microreactors, gas-liquid interface engineering and continuous operation configuration (Raheja et al., 2026). In acetone–butanol–ethanol (ABE) fermentation, coupling gas stripping with pervaporation increased the butanol concentration from approximately 10–12 g/L in the broth to 482.55 g/L in the membrane permeate, allowing removal of the energy-intensive beer column. The integrated gas stripping–pervaporation–distillation process required 24.83 MJ/kg butanol, which was further reduced to 23.07 MJ/kg through pinch-based heat recovery only 29.2% of the energy demand reported for conventional distillation. These findings demonstrate that in situ concentration and heat integration can substantially reduce the downstream energy burden of recovering low-titre microbial products (Cai et al., 2016). Moreover, in silico experiments combining density functional theory, molecular simulations, and machine learning will aid the process of catalyst design and development (Wen et al., 2025). Likewise, policy frameworks, carbon pricing and focused investments will be crucial for commercializing these technologies. Eventually, converting CO₂ from an environmental liability into a renewable feedstock will establish a robust circular carbon economy, reforming global carbon management strategies.

5 Conclusion

The development of CO₂ transformation has emerged as a cornerstone of sustainable carbon management. Catalytic, electrochemical, biological and photochemical techniques have represented a noteworthy progress in transforming CO₂ into fuels and intermediates or non-natural products. Apart from that the scalability and energy efficiency remain critical hurdles in the pathways developed. Biological strategies utilize both natural organisms and engineered systems, providing an integrated approach of carbon fixation with renewable energy inputs and metabolic tailoring. Bioelectrochemical systems, in particular, demonstrate hybrid approaches that merge biological selectivity with electrochemical precision. CO₂ can serve as a keystone for next-generation products, such as carboxylated aromatics, advanced solvents, and functional polymers, with greater performance as well as sustainability. The application of CO₂ to novel non-natural products used in pharmaceuticals and biomedical engineering further expands the significance of CO₂ as a building blocks in healthcare and biotechnology. CO₂ conversion is evolving into a multidisciplinary field with remarkable industrial and societal impact. However, a successful implementation depends on integrating diverse platforms, optimizing energy inputs, and aligning with policy frameworks that incentivize carbon valorisation. By positioning CO₂ as a resource rather than a liability, these emerging techniques will pave the way toward a circular carbon economy, supporting environmental sustainability.

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Footnotes

Edited by: Jayato Nayak, Mahindra University, India

Reviewed by: Akeem Adeyemi Oladipo, Eastern Mediterranean University, Türkiye

Ajit Sharma, Lovely Professional University, India

Domingo César Carrascal-Hernández, Universidad del Norte, Colombia