학술논문
Actinobacterial chalkophores: the biosynthesis of hazimycins.
Document Type
Academic Journal
Author
Matsuda K; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan. kematsuda@pharm.hokudai.ac.jp.; Maruyama H; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.; Imachi K; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.; Ikeda H; Technology Research Association for Next generation natural products chemistry, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.; Wakimoto T; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan. wakimoto@pharm.hokudai.ac.jp.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0151115 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1881-1469 (Electronic) Linking ISSN: 00218820 NLM ISO Abbreviation: J Antibiot (Tokyo) Subsets: MEDLINE
Subject
Language
English
Abstract
Copper is a transition metal element with significant effects on the morphological development and secondary metabolism of actinobacteria. In some microorganisms, copper-binding natural products are employed to modulate copper homeostasis, although their significance in actinobacteria remains largely unknown. Here, we identified the biosynthetic genes of the diisocyanide natural product hazimycin in Kitasatospora purpeofusca HV058, through gene knock-out and heterologous expression. Biochemical analyses revealed that hazimycin A specifically binds to copper, which diminishes its antimicrobial activity. The presence of a set of putative importer/exporter genes surrounding the biosynthetic genes suggested that hazimycin is a chalkophore that modulates the intracellular copper level. A bioinformatic survey of homologous gene cassettes, as well as the identification of two previously unknown hazimycin-producing Streptomyces strains, indicated that the isocyanide-based mechanism of copper homeostasis is prevalent in actinobacteria.
(© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)
(© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)