Regulation mechanism and bioactivity characteristic of surfactin homologues with C14 and C15 fatty acid chains

Microb Cell Fact. 2024 Mar 27;23(1):94. doi: 10.1186/s12934-024-02373-6.

Abstract

Background: Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities.

Results: In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14-C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14-C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities.

Conclusion: This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure-activity relationships of surfactin and other lipopeptide compounds.

Keywords: Bioactivity; Homologues; Regulation mechanism; Surfactin; Transcriptome analysis.

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacillus subtilis / genetics
  • Fatty Acids* / metabolism
  • Glutamic Acid / metabolism
  • Lipopeptides
  • Peptides, Cyclic / chemistry
  • Surface-Active Agents* / metabolism

Substances

  • Fatty Acids
  • Surface-Active Agents
  • Glutamic Acid
  • Lipopeptides
  • Anti-Bacterial Agents
  • Peptides, Cyclic

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