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Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity

Title
Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity
Authors
Kim, EunjiShin, Yern-HyerkKim, Tae HoByun, Woong SubCui, JinshengDu, Young EunLim, Hyung-JuSong, Myoung ChongKwon, An SungKang, Sang HyeonShin, JongheonLee, Sang KookJang, JichanOh, Dong-ChanYoon, Yeo Joon
Ewha Authors
윤여준송명종
SCOPUS Author ID
윤여준scopus; 송명종scopus
Issue Date
2019
Journal Title
BIOMOLECULES
ISSN
2218-273XJCR Link
Citation
BIOMOLECULES vol. 9, no. 11
Keywords
ohmyungsamycinmarine natural productnonribosomal peptide synthetasebiosynthetic gene clusterantituberculosis activity
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
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.
DOI
10.3390/biom9110672
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자연과학대학 > 화학·나노과학전공 > Journal papers
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