%0 Journal Article
%T Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity
%J Biomolecules | An Open Access Journal from MDPI
%D 2019
%R https://doi.org/10.3390/biom9110672
%X 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, ¦Â-hydroxy- l-phenylalanine ( ¦Â-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 ¦Â-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. View Full-Tex
%U https://www.mdpi.com/2218-273X/9/11/672