Engineering and Scalable Production of Next-Generation Antimicrobials

Antimicrobial resistance (AMR) is reducing the effectiveness of established antibiotics and increasing the need for new antimicrobial products and more efficient development strategies. Microorganisms are important both as sources of antimicrobial compounds—including antimicrobial peptides, bacteriocins, peptide-like natural products, and antibiotics—and as production platforms for pharmaceutical products and intermediates. However, the translation of promising antimicrobial candidates into scalable products remains challenging because of low titers, product variability, instability, scale-up limitations, and the costs associated with downstream processing and formulation.Advances in metabolic engineering, synthetic biology, strain development, and bioprocess optimization are creating new opportunities to connect antimicrobial discovery with reliable and economically viable production. At the same time, combining peptides with conventional antibiotics may improve antimicrobial activity, address resistance mechanisms, and reduce the required dose of individual agents. However, further research is needed to integrate product discovery, molecular engineering, manufacturing, analytical characterization, and biological performance testing within a coherent development framework.GoalThis Research Topic aims to highlight high level research on the discovery, engineering, production, characterization, and evaluation of next-generation antimicrobial products. Particular emphasis will be placed on microbial and other biologically derived antimicrobial peptides, bacteriocins, peptide-like natural products, antibiotics, and peptide–antibiotic combinations.The Research Topic will bring together studies that address the complete development pathway, from structure–function relationships and mechanism of action to strain improvement, fermentation, downstream processing, formulation, and performance testing. Contributions should demonstrate clear relevance to improving antimicrobial potency, manufacturability, reproducibility, stability, scalability, or resistance management.ScopeWe welcome contributions addressing the development of antimicrobial peptides, bacteriocins, peptide-like natural products, microbially produced antibiotics, and related products, with an emphasis on approaches that support translation toward robust and scalable applications. Studies involving plant- or animal-derived antimicrobial peptides may also be considered where they contribute to the engineering, production, characterization, or development of next-generation antimicrobial products.Themes include, but are not limited to:- Antimicrobial discovery and characterization: Discovery, production, structure–function analysis, mechanism of action, stability, and activity assessment of antimicrobial peptides, bacteriocins, peptide-like natural products, and microbial antibiotics.- Engineering of antimicrobial products and production hosts: Molecular engineering and host selection involving bacteria, yeasts, filamentous fungi, or other suitable systems to improve activity, stability, secretion, yield, productivity, genetic stability, and product homogeneity.- Microbial biotechnology and bioprocess development: Metabolic engineering, synthetic biology, design-build-test-learn workflows, fermentation optimization, process monitoring, scale-up, process robustness, and process intensification for antimicrobial production.- Downstream processing, formulation, and quality assessment: Capture, purification, stabilization, drying, formulation, and analytical strategies addressing identity, purity, potency, impurities, batch comparability, cost, and relevant quality attributes.- Synergy-driven antimicrobial development: Experimental and computational approaches for identifying and validating combinations of antimicrobial peptides or other biologically derived products with conventional antibiotics, including mechanism-informed combination design, anti-biofilm activity, potentiation, and permeabilization.- Resistance-aware evaluation and translation: Comparative assessment of single-agent and combination treatments, resistance development, reproducibility across experimental systems, and links between manufacturing conditions, formulation, antimicrobial activity, and combination performance.- Computational, analytical, and high-throughput approaches: Methods that accelerate antimicrobial discovery, product optimization, process development, activity prediction, or the evaluation of structure, potency, synergy, and resistance-related outcomes. Topic editors: Celia Fortuna R., Luan Luong Chu, Maurice George Ekpenyong Source: https://www.frontiersin.org/research-topics/79396/engineering-and-scalable-production-of-next-generation-antimicrobials