Systematic optimization for production of the anti-MRSA antibiotics WAP-8294A in an engineered strain of Lysobacter enzymogenes

Authors

Xusheng Chen, Jiangnan University & University of Nebraska- Lincoln
Shanren Li, University of Nebraska- Lincoln
Lingjun Yu, University of Nebraska- Lincoln
Amanda Miller, University of Nebraska- Lincoln
Liangcheng Du, University of Nebraska - LincolnFollow

ORCID IDs

https://orcid.org/0000-0003-4048-1008

Date of this Version

8-13-2019

Citation

2019 The Authors.

Comments

Production of the anti-MRSA antibiotics WAP-8294A

Abstract

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.