Microbial synthesis of bacitracin: Recent progress, challenges, and prospects

Jiang Zhu; Shiyi Wang; Cheng Wang; Zhi Wang; Gan Luo; Junhui Li; Yangyang Zhan; Dongbo Cai; Shouwen Chen

doi:10.1016/j.synbio.2023.03.009

Microbial synthesis of bacitracin: Recent progress, challenges, and prospects

Synth Syst Biotechnol. 2023 Apr 10;8(2):314-322. doi: 10.1016/j.synbio.2023.03.009. eCollection 2023 Jun.

Authors

Jiang Zhu¹, Shiyi Wang¹, Cheng Wang¹, Zhi Wang², Gan Luo³, Junhui Li³, Yangyang Zhan¹, Dongbo Cai¹, Shouwen Chen¹

Affiliations

¹ State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Sciences, Hubei University, Wuhan, 430062, PR China.
² Hubei Provincial Key Laboratory of Industrial Microbiology, Key Laboratory of Fermentation Engineering (Ministry of Education), School of Food and Biological Engineering, Hubei University of Technology, Wuhan, 430068, Hubei, PR China.
³ Lifecome Biochemistry Co. Ltd, Nanping, 353400, PR China.

Abstract

Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare. Bacitracin is an important antibacterial natural product predominantly produced by Bacillus licheniformis and Bacillus subtilis, and it is characterized by a broad antimicrobial spectrum, strong activity and low resistance, thus bacitracin is extensively applied in animal feed and veterinary medicine industries. In recent years, various strategies have been proposed to improve bacitracin production. Herein, we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism, to provide a theoretical basis for bacitracin overproduction. The metabolic engineering strategies applied for bacitracin production are explored, including improving substrate utilization, using an enlarged precursor amino acid pool, increasing ATP supply and NADPH generation, and engineering transcription regulators. We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin. Finally, the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.

Keywords: Bacillus; Bacitracin; Fermentation process; Metabolic engineering; Metabolic regulation.

Publication types

Review