Recent Advances and Future Perspectives in the Biomanufacturing of Lipopeptides: From Strain Engineering to Industrial Applications.

Microbial lipopeptides are amphiphilic natural products in which the peptide scaffold and the fatty-acyl chain jointly determine interfacial behavior, membrane activity, and biological specificity. Bacillus species remain the most developed industrial platforms owing to their ability to produce surfactin-, iturin-, and fengycin/plipastatin-type cyclic lipopeptides via modular nonribosomal peptide synthetase (NRPS) systems. Recent efforts have moved beyond strain screening and single-gene overexpression toward integrated engineering strategies that couple pathway activation with precursor supply, developmental regulation, exporter capacity, membrane tolerance, fermentation control, and downstream recovery. Integrated strain and process engineering improve yield and robustness, whereas programmable NRPS editing enables deliberate modification of amino-acid composition and fatty-acyl chain features. Application specificity remains a key consideration. Agricultural and environmental uses may accommodate functional mixtures provided batch-to-batch consistency is demonstrated. In contrast, food, cosmetic, and biomedical applications demand tighter compositional control, toxicological evaluation, and regulatory compliance. These differing requirements underscore that product profile and use context are as critical as titer in the successful biomanufacturing of lipopeptides.