Poly-γ-Glutamic Acid Production by Engineering a DegU Quorum-Sensing Circuit in Bacillus subtilis

• DOI: 10.1021/acssynbio.2c00464
• Publication Date: 2022-11-23T12:19:16Z
• Authors: Liu-xiu Hu; Ming Zhao; Wen-song Hu; Meng-jie Zhou; Jun-bao Huang; Xi-lin Huang; Xu-li Gao; Ya-ni Luo; Chuang Li; Kun Liu; Zheng-lian Xue; Yan Liu
• Keywords: Bioproduction; Metabolic Engineering; Synthetic Biology

As a natural biological macromolecule, γ-polyglutamic acid (γ-PGA) plays significant role in medicine, food, and cosmetic industries owing to its unique properties of biocompatibility, biodegradability, water solubility, viscosity. Although many strategies have been adopted increase the yield γ-PGA Bacillus subtilis, effectiveness these common approaches is not high because strong viscosity affects cell growth. However, dynamic regulation based on quorum sensing (QS) has extensively applied as fundamental tool for fine-tuning gene expression reaction changes density without adding expensive inducers. A modular PhrQ-RapQ-DegU QS system developed promoter PD4, which upregulated by phosphorylated DegU (DegU-P). In this study, first, we analyzed DegU-based B. subtilis 168. We constructed library different abilities, selected suitable promoters from library, performed mutation screening degU region. Furthermore, dynamically control synthesis BS168. Cell growth efficient target product can be balanced system. Our adjustment approach increased 6.53-fold that static 3 L bioreactor, verified strategy. summary, successfully integrated with biocatalytic functions achieve metabolic pathway BS168, stretched large number microorganisms fine-tune enhance production metabolites.