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- Title
Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions.
- Authors
Kim, Eunji; Du, Young Eun; Ban, Yeon Hee; Shin, Yern-Hyerk; Oh, Dong-Chan; Yoon, Yeo Joon
- Abstract
Ohmyungsamycins (OMSs) A and B are cyclic depsipeptides produced by marine Streptomyces strains, which are synthesized by a non-ribosomal peptide synthetase. Notably, OMS A exhibits more potent activity against Mycobacterium tuberculosis and human cancer cells than OMS B. The substrate promiscuous adenylation (A) domain in the second module of OMS synthetase recruits either L-Val or L-Ile to synthesize OMSs A and B, respectively. Engineering of the substrate-coding residues of this A domain increased OMS A production by 1.2-fold, coupled with a drastic decrease in OMS B production. Furthermore, the culture conditions (sea salt concentration, inoculum size, and the supply of amino acids to serve as building blocks for OMS) were optimized for OMS production in the wild-type strain. Finally, cultivation of the A2-domain-engineered strain under the optimized culture conditions resulted in up to 3.8-fold increases in OMS A yields and an 8.4-fold decrease in OMS B production compared to the wild-type strain under the initial culture conditions.
- Subjects
MYCOBACTERIUM tuberculosis; CONOTOXINS; SEA salt; DEPSIPEPTIDES; AMINO acids; CANCER cells
- Publication
Frontiers in Microbiology, 2021, Vol 11, pN.PAG
- ISSN
1664-302X
- Publication type
Article
- DOI
10.3389/fmicb.2021.626881