View : 48 Download: 0
Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity
- Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity
- Kim, Eunji; Shin, Yern-Hyerk; Kim, Tae Ho; Byun, Woong Sub; Cui, Jinsheng; Du, Young Eun; Lim, Hyung-Ju; Song, Myoung Chong; Kwon, An Sung; Kang, Sang Hyeon; Shin, Jongheon; Lee, Sang Kook; Jang, Jichan; Oh, Dong-Chan; Yoon, Yeo Joon
- Ewha Authors
- 윤여준; 송명종
- SCOPUS Author ID
- 윤여준; 송명종
- Issue Date
- Journal Title
- BIOMOLECULES vol. 9, no. 11
- ohmyungsamycin; marine natural product; nonribosomal peptide synthetase; biosynthetic gene cluster; antituberculosis activity
- SCIE; SCOPUS
- Document Type
- The cyclic depsipeptides ohmyungsamycin (OMS) A (1) and B (2), isolated from the marine-derived Streptomyces sp. SNJ042, contain two non-proteinogenic amino acid residues, beta-hydroxy-L-phenylalanine (beta-hydroxy-L-Phe) and 4-methoxy-L-tryptophan (4-methoxy-L-Trp). Draft genome sequencing of Streptomyces sp. SNJ042 revealed the OMS biosynthetic gene cluster consisting of a nonribosomal peptide synthetase (NRPS) gene and three genes for amino acid modification. By gene inactivation and analysis of the accumulated products, we found that OhmL, encoding a P450 gene, is an l-Phe beta-hydroxylase. Furthermore, OhmK, encoding a Trp 2,3-dioxygenase homolog, and OhmJ, encoding an O-methyltransferase, are suggested to be involved in hydroxylation and O-methylation reactions, respectively, in the biosynthesis of 4-methoxy-L-Trp. In addition, the antiproliferative and antituberculosis activities of the OMS derivatives dehydroxy-OMS A (4) and demethoxy-OMS A (6) obtained from the mutant strains were evaluated in vitro. Interestingly, dehydroxy-OMS A (4) displayed significantly improved antituberculosis activity and decreased cytotoxicity compared to wild-type OMS A.
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.