Next Article in Journal
Illuminating Clues of Cancer Buried in Prostate MR Image: Deep Learning and Expert Approaches
Next Article in Special Issue
The Antitumor Agent Ansamitocin P-3 Binds to Cell Division Protein FtsZ in Actinosynnema pretiosum
Previous Article in Journal
Elicitors and Pre-Fermentative Cold Maceration: Effects on Polyphenol Concentration in Monastrell Grapes and Wines
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomolecules
Volume 9
Issue 11
10.3390/biom9110672
biomolecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

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

by
Eunji Kim
1,†,
Yern-Hyerk Shin
2,†,
Tae Ho Kim
3,
Woong Sub Byun
2,
Jinsheng Cui
2,
Young Eun Du
2,
Hyung-Ju Lim
2,
Myoung Chong Song
1,
An Sung Kwon
4,
Sang Hyeon Kang
4,
Jongheon Shin
2,
Sang Kook Lee
2,
Jichan Jang
3,
Dong-Chan Oh
2,* and
Yeo Joon Yoon
1,*
1
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea
2
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea
3
Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju 52828, Korea
4
iNtRON Biotechnology, Inc., Seongnam-si, Gyeonggi-do 13202, Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2019, 9(11), 672; https://doi.org/10.3390/biom9110672
Submission received: 19 September 2019 / Revised: 26 October 2019 / Accepted: 28 October 2019 / Published: 30 October 2019
(This article belongs to the Special Issue Recent Advance of Actinomycetes)
Browse Figures
Versions Notes

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, β-hydroxy-l-phenylalanine (β-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 β-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.
Keywords: ohmyungsamycin; marine natural product; nonribosomal peptide synthetase; biosynthetic gene cluster; antituberculosis activity ohmyungsamycin; marine natural product; nonribosomal peptide synthetase; biosynthetic gene cluster; antituberculosis activity

Share and Cite

MDPI and ACS Style

Kim, E.; Shin, Y.-H.; Kim, T.H.; Byun, W.S.; Cui, J.; Du, Y.E.; Lim, H.-J.; Song, M.C.; Kwon, A.S.; Kang, S.H.; et al. Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity. Biomolecules 2019, 9, 672. https://doi.org/10.3390/biom9110672

AMA Style

Kim E, Shin Y-H, Kim TH, Byun WS, Cui J, Du YE, Lim H-J, Song MC, Kwon AS, Kang SH, et al. Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity. Biomolecules. 2019; 9(11):672. https://doi.org/10.3390/biom9110672

Chicago/Turabian Style

Kim, Eunji, Yern-Hyerk Shin, Tae Ho Kim, Woong Sub Byun, Jinsheng Cui, Young Eun Du, Hyung-Ju Lim, Myoung Chong Song, An Sung Kwon, Sang Hyeon Kang, and et al. 2019. "Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity" Biomolecules 9, no. 11: 672. https://doi.org/10.3390/biom9110672

APA Style

Kim, E., Shin, Y.-H., Kim, T. H., Byun, W. S., Cui, J., Du, Y. E., Lim, H.-J., Song, M. C., Kwon, A. S., Kang, S. H., Shin, J., Lee, S. K., Jang, J., Oh, D.-C., & Yoon, Y. J. (2019). Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity. Biomolecules, 9(11), 672. https://doi.org/10.3390/biom9110672

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop