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Exploring the metabolic burden of surfactin biosynthesis and the metabolic costs of srfA operon expression in Bacillus subtilis.

Created on 20 Jun 2026

Authors

Elvio Henrique Benatto Perino, Eric Hiller, Maliheh Vahidinasab, Sandra Moneta, Bahar Abrishamchi, Kowsala Nagendran, Philipp Hubel, Jens Pfannstiel, Rudolf Hausmann

Published in

Microbial cell factories. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

The biosynthesis of surfactin, a potent lipopeptide biosurfactant produced by Bacillus subtilis, imposes a significant metabolic burden on the host organism. Understanding the metabolic costs associated with surfactin production, specifically the ATP demand and precursor diversion resulting from the expression of the large srfAA-AD operon (srfA operon), is crucial for optimizing production strains. In this study, the metabolic burden and growth impacts associated with surfactin biosynthesis in B. subtilis were quantitatively evaluated by comparing a reference surfactin-producing strain (BMV9) with two mutant strains: BMV12, which lacks the srfA operon, and BMV33, which retains the srfA operon but lacks the sfp gene. Our analysis included theoretical calculations of ATP and NADPH + H+ requirements for de novo surfactin synthesis, and we measured growth behavior and carbon and nitrogen source consumption. Results indicated that surfactin production significantly reduces biomass yield (YX/S) and specific growth rates due to the metabolic costs of expressing the non-ribosomal peptide synthetase (NRPS) and the diversion of key precursors. Notably, BMV12 exhibited higher growth rates compared to the surfactin-producing strain. Proteome analyses further revealed differential protein abundance in non-surfactin-producing strains, indicating altered metabolic pathways that may relieve the metabolic burden associated with surfactin synthesis. These findings highlight the complex trade-offs between secondary metabolite production and cellular growth, providing a foundation for metabolic engineering strategies aimed at optimizing surfactin yields while minimizing metabolic costs.

PMID:
42321830
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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