Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions
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 a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.626881/full |
| _version_ | 1818949969925636096 |
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| author | Eunji Kim Young Eun Du Yeon Hee Ban Yern-Hyerk Shin Dong-Chan Oh Yeo Joon Yoon |
| author_facet | Eunji Kim Young Eun Du Yeon Hee Ban Yern-Hyerk Shin Dong-Chan Oh Yeo Joon Yoon |
| author_sort | Eunji Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T09:11:09Z |
| format | Article |
| id | doaj.art-c0d7f875e1364e19961da6c18b8861d1 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T09:11:09Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-c0d7f875e1364e19961da6c18b8861d12022-12-21T19:45:34ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-02-011210.3389/fmicb.2021.626881626881Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture ConditionsEunji KimYoung Eun DuYeon Hee BanYern-Hyerk ShinDong-Chan OhYeo Joon Yoon0atural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, South KoreaOhmyungsamycins (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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.626881/fullohmyungsamycinnon-ribosomal peptide synthetaseadenylation domain engineeringsite-directed mutagenesisculture condition optimization |
| spellingShingle | Eunji Kim Young Eun Du Yeon Hee Ban Yern-Hyerk Shin Dong-Chan Oh Yeo Joon Yoon Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions Frontiers in Microbiology ohmyungsamycin non-ribosomal peptide synthetase adenylation domain engineering site-directed mutagenesis culture condition optimization |
| title | Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions |
| title_full | Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions |
| title_fullStr | Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions |
| title_full_unstemmed | Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions |
| title_short | Enhanced Ohmyungsamycin A Production via Adenylation Domain Engineering and Optimization of Culture Conditions |
| title_sort | enhanced ohmyungsamycin a production via adenylation domain engineering and optimization of culture conditions |
| topic | ohmyungsamycin non-ribosomal peptide synthetase adenylation domain engineering site-directed mutagenesis culture condition optimization |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.626881/full |
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