No 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.

A genomic and spectroscopic signature-based search revealed a cycloaromatized enediyne, jejucarboside A (1), from a marine actinomycete strain. The structure of 1 was determined as a new cyclopenta[a]indene glycoside bearing carbonate functionality by nuclear magnetic resonance, high-resolution mass spectrometry (MS), MS/MS, infrared spectroscopy, and a modified Mosher's method. An iterative enediyne synthase pathway has been proposed for the putative biosynthesis of 1 by genomic analysis. Jejucarboside A exhibited cytotoxicity against the HCT116 colon carcinoma cells.

The increase in drug-resistant Mycobacterium abscessus, which has become resistant to existing standard-of-care agents, is a major concern, and new antibacterial agents are strongly needed. In this study, we introduced etamycin that showed an excellent activity against M. abscessus. We found that etamycin significantly inhibited the growth of M. abscessus wild-type strain, three subspecies, and clinical isolates in vitro and inhibited the growth of M. abscessus that resides in macrophages without cytotoxicity. Furthermore, the in vivo efficacy of etamycin in the zebrafish (Danio rerio) infection model was greater than that of clarithromycin, which is recommended as the core agent for treating M. abscessus infections. Thus, we concluded that etamycin is a potential anti-M. abscessus candidate for further development as a clinical drug candidate.

Formicins A−C (1−3) were discovered from Streptomyces sp. associated with wood ants. The structures of 1 and 2 were elucidated as indenone thioesters bearing N-acetylcysteamine based on spectroscopic analysis. The configurations of 1−3 were determined by the analysis of ROESY correlations, the phenylglycine methyl ester method, and chemical derivatization from 3 to 2. Formicin A inhibited the growth of human triple-negative breast cancer cells by regulating the liver kinase B1-mediated AMPK signaling pathway.