Metabolomic analysis of the effect glutamate on fengycin-overproducing Bacillus subtilis ATCC 21332 with an enhanced fatty acid synthesis pathway

Fengycin is a of cyclic lipopeptide with antifungal, antitumor and adhesion-preventing activities, with great application potential in biological control, medicine and industry. However, the fermentation yield of fengycin is inadequate, which limits its wider application. In this study, key modules for enhanced fatty acid synthesis were cloned singly and in combination, and the suitability of these modules for B. subtilis ATCC 21332 was investigated. We constructed the engineered strain BSA034, which exhibited a 3-fold increase of fengycin titer, which reached 442.51 mg/L. Reverse transcription and quantitative PCR (RT-qPCR) revealed the effect of enhanced branched-chain fatty acid synthesis on the expression level of the fen operon in B. subtilis ATCC 21332, which significantly contributed to the increase of fengycin production. The exogenous supplementation of glutamate further increased the fengycin titer of BSA034 to 657.55 mg/L. Further comparative metabolomic analysis revealed that glutamate mainly promoted the membrane transport of BSA034, which provides a rational basis for further improving the titer of fengycin in the future. •BSA034 was constructed by over-expressing fabHB from BSA00 and fabF from FZB42 in BSA00, its fengycin titer is 442.51 mg/L.•RT-qPCR was used to evaluate the expression of the fen operon used to synthesize fengycin in BSA034.•The fengycin titer of BSA034 was further increased to 657.55 mg/L by exogenous glutamate supplementation.•The metabolomic analysis showed that glutamate supplementation promoted the membrane transport of BSA034.