ComQXPA Quorum Sensing Dynamic Regulation Enhanced Fengycin Production of .

J Nat Prod

State Key Laboratory of Synthetic Biology, School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, PR China.

Published: April 2025


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Article Abstract

Fengycin is an antifungal drug that could be used as a biocontrol agent if it could be produced in high amounts. The ComQXPA quorum sensing (QS) system is a natural mechanism, regulating cell density-dependent behaviors in . This study employed the QS-targeted promoter to express the gene cluster in , coupling the ComQXPA system to produce fengycin. Mutations in the ComA regulatory protein-binding site RE3 exhibited a 2.45-fold increase in promoter expression intensity and resulted in an elevation of fengycin production from 489 to 1832 mg/L, a 2.74-fold enhancement. Transcriptomic analysis revealed the upregulation of genes associated with carbon source uptake and utilization and metabolic pathways related to amino acids and fatty acids, which are precursors for fengycin synthesis. Additionally, knockout of and increased fengycin production to 3190 mg/L. In a coculture system constructed with , fengycin production reached 4005 mg/L. This work provides a strategy for dynamically regulating fengycin synthesis.

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http://dx.doi.org/10.1021/acs.jnatprod.4c01328DOI Listing

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