Analysis of glutamate-dependent mechanism and optimization of fermentation conditions for polyglutamic acid production by Bacillus subtilis SCP017-03

Abstract Poly-gamma-glutamic acid (γ-PGA) is mainly synthesized by glutamate-dependent strains in the manufacturing industry. Therefore, understanding glutamate-dependent mechanisms is imperative. In this study, we first systematically analyzed the response of Bacillus subtilis SCP017-03 to glutamate addition by comparing transcriptomics and protein genomics. The introduction of glutamate substantially altered the gene expression within the central metabolic pathway of cellular carbon. Most genes in the pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and energy-consuming phase of the glycolysis pathway (EMP) were down-regulated, whereas genes in the energy-producing phase of glycolysis and those responsible for γ-PGA synthesis were up-regulated. Based on these findings, the fermentation conditions were optimized and the γ-PGA production was improved by incorporating oxygen carriers. In a batch-fed fermentor with glucose, the γ-PGA yield reached 95.2 g/L, demonstrating its industrial production potential. This study not only elucidated the glutamic acid dependence mechanism of Bacillus subtilis but also identified a promising metabolic target for further enhancing γ-PGA production.