Systematic optimization for production of the anti‐MRSA antibiotics WAP‐8294A in an engineered strain of Lysobacter enzymogenes. Issue 6 (14th September 2019)

• Record Type: Journal Article
• Authors: Chen, Xusheng; Li, Shanren; Yu, Lingjun; Miller, Amanda; Du, Liangcheng
• Is Part Of: Microbial biotechnology. Volume 12:Issue 6(2019:Nov.)
• Page Start: 1430
• Page End: 1440
• Publication Date: 2019-09-14
• Subjects: Microbial biotechnology -- Periodicals; Biotechnology; Microbiology; 660.62
• DOI: 10.1111/1751-7915.13484
• Languages: English
• ISSNs: 1751-7915

Abstract

Summary: WAP‐8294A is a group of cyclic lipodepsipeptides and considered as the first‐in‐class new chemical entity with potent activity against methicillin‐resistant Staphylococcus aureus . One of the roadblocks in developing the WAP‐8294A antibiotics is the very low yield in Lysobacter . Here, we carried out a systematic investigation of the nutritional and environmental conditions in an engineered L . enzymogenes strain for the optimal production of WAP‐8294A. We developed an activity‐based simple method for quick screening of various factors, which enabled us to optimize the culture conditions. With the method, we were able to improve the WAP‐8294A yield by 10‐fold in small‐scale cultures and approximately 15‐fold in scale‐up fermentation. Additionally, we found the ratio of WAP‐8294A2 to WAP‐8294A1 in the strains could be manipulated through medium optimization. The development of a practical method for yield improvement in Lysobacter will facilitate the ongoing basic research and clinical studies to develop WAP‐8294A into true therapeutics. Abstract : This manuscript described a simple method for yield improvement of a group of potent anti‐MRSA natural products (WAP‐8294As) in a genus of underexplored microorganisms, Lysobacter . Through a systematic investigation of the optimal culture conditions for WAP‐8294As production in an engineered Lysobacter strain, the yield of the antibiotics increased by 10–15 fold.