TY - JOUR
T1 - Systematic optimization for production of the anti-MRSA antibiotics WAP-8294A in an engineered strain of Lysobacter enzymogenes
AU - Chen, Xusheng
AU - Li, Shanren
AU - Yu, Lingjun
AU - Miller, Amanda
AU - Du, Liangcheng
N1 - Funding Information:
We thank R. Cerny and K. Wulser for technical assistance. This work was supported in part by a Revision Award from UNL. X. C. was partly supported by China Scholarship Council, and A. M. partly by the McNair Graduate Student Support Fellowship.
Publisher Copyright:
© 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1111/1751-7915.13484
DO - 10.1111/1751-7915.13484
M3 - Article
C2 - 31520522
AN - SCOPUS:85073592721
SN - 1751-7907
VL - 12
SP - 1430
EP - 1440
JO - Microbial Biotechnology
JF - Microbial Biotechnology
IS - 6
ER -