Precision Fermentation: Engineering Next-Generation Microbial Platforms for Sustainable Production

For more than a century, the industrial production of chemicals, fuels, foods, and medicines has relied on wild-type microbial, plant, and animal hosts. While these natural processes are functional, they are not always energy-efficient, environmentally sustainable, or economically viable at a global scale.Precision fermentation addresses these limitations by leveraging recombinant technology, modern molecular biology, and computational science to transform single-cell organisms (such as yeast and bacteria) into programmable cellular factories. By equipping host cells with the enzymatic tools to run natural and non-natural biochemical pathways, and by refining the fermentation process through large-scale data analysis and AI-driven control, precision fermentation has the paradoxical potential to make known microbial processes optimal while opening the door to entirely new production profiles and schemes.The central technical challenge of precision fermentation is engineering robust host cells that can express target enzymes, sustain demanding metabolic pathways, and deliver high-purity products at an industrial scale. Submerged culture fermentation has been practiced for nearly a century and scales predictably when feedstocks and products are water-soluble, moving from pilot to commercial scale in manageable steps. However, the picture changes significantly when feedstocks or products are not water-soluble: handling slurries and extracting products from cells or culture broth introduces engineering complexity that grows with scale. At very large volumes, additional challenges arise around waste and process-water disposal, feedstock consistency, and the maintenance of high-quality seed cultures. While biological processes are inherently safer than chemical alternatives due to operating near neutral pH and sub-boiling temperatures, deploying genetically modified organisms (GMOs) at commercial scale requires rigorous biological containment engineering and site permitting to ensure global viability and public acceptance.This Research Topic brings together current work, enabling technologies, and open questions across the entire value chain of precision fermentation — from host-cell engineering and pathway design to bioprocess development and sector-specific applications. We welcome Original Research, Reviews, Mini-Reviews, Methods, Perspectives, and Opinion articles from academic and industrial researchers addressing the benefits, challenges, and methodologies of precision fermentation across the following core themes:o Fuels, Chemicals, and Intermediates: Engineering host organisms (such as Zymomonas mobilis and Saccharomyces cerevisiae) for biofuels, ethanol, 2,3- and 1,4-butanediol, formic acid, isoprene, and other chemical industry intermediates, including biomass-degrading enzymes from lignocellulosic feedstocks.o Food Technology and Ingredients: Increased productivity of recombinant enzymes and additives for food and beverage manufacturing, including dairy production additives, heme for meat alternatives, dietary fats, sweeteners, and pigments.o Agricultural Technology: Enhanced production of rhizosphere and other plant/soil-enhancing microorganisms at scale for maximum soil enrichment and agricultural sustainability.o Polymers and Biomaterials: Production of microbial biodegradable polymers, spider silk, and collagen, alongside the downstream recovery and separation challenges these products present.o Pharmaceuticals and Health Products: Production of vaccines, probiotics, antibiotics, therapeutic proteins, and high-value natural products from non-native commercial hosts, with particular attention to purity, process robustness, separation costs, and scalable post-translational modifications.o Enabling Tools and Bioprocess Control: Application of ML and AI for fermentation optimisation; cofactor and electron-transfer engineering (especially in metalloenzymes); cell-free and engineered-translation production systems; engineered mRNA/tRNA for non-natural amino acids; CRISPR-Cas9 and other tools for large gene-set assembly; and advanced fermentation equipment, process safety, and GMO containment. Topic editors: Michael E. Himmel, Lilly Amore, Stephen R Decker, Ze-Chun Yuan Source: https://www.frontiersin.org/research-topics/83280/precision-fermentation-engineering-next-generation-microbial-platforms-for-sustainable-production