Increasing fengycin production by strengthening the fatty acid synthesis pathway and optimizing fermentation conditions

Abstract In the present work, Bacillus subtilis 168 was engineered as a cell factory for fengycin production by activating its dormant native fengycin synthetase. Initially, the sfp gene from Bacillus amyloliquefaciens FZB42 was introduced into B. subtilis 168 to activate fengycin biosynthesis. Then, the original promoter of the degQ gene was replaced with the P43 promoter, resulting in strain 168DS. The fengycin production of 168DS increased to 10.40 mg/L in flask culture, realizing significant fengycin synthesis starting from zero. Subsequently, the birA, acs and accACD genes were overexpressed in the engineered strain 168DS to enhance the yield of fengycin, resulting in strain 168DSABA. The fengycin production of 168DSABA increased to 24.70 mg/L in flask culture, representing a 137% increase over the parental strain 168DS. Additionally, we also attempted to increase fengycin production by optimizing the medium components and fermentation conditions. This optimization strategy increased the fengycin production from 24.70 to 130.10 mg/L. Subsequent metabolomic analysis revealed the underlying reasons for the increase of fengycin production. This strategy provides the possibility to increase the industrial production of fengycin and promote its applications by reducing its price.