Journal
MOLECULAR BIOSYSTEMS
Volume 7, Issue 3, Pages 920-927Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c0mb00237b
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Funding
- Ministry of Science and Technology [973, 863]
- National Science Foundation of China
- China Postdoctoral Foundation
- Ministry of Education
- Science and Technology Commission of Shanghai Municipality
- Shanghai Leading Academic Discipline Project [B203]
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Muraymycin, a potent translocase I inhibitor with clinical potential, is produced by Streptomyces sp. NRRL 30471. The structure of muraymycin is highly unusual and contains the hexahydro-2-imino-4-pyrimidylglycyl moiety (epicapreomycidine) and an ureido bond. Here we report the identification of the muraymycin gene cluster from Streptomyces sp. NRRL 30471. Sequencing analysis of a 43.4-kb contiguous region revealed 33 ORFs, 26 of which were proposed to be involved in muraymycin biosynthesis. Independent targeted inactivation of mur16 and mur17 directly abolished muraymycin production, demonstrating the role of the genes essential for muraymycin biosynthesis. These data provide insights into the molecular mechanisms for muraymycin biosynthesis, and lay a foundation for the generation of muraymycin derivatives with enhanced bioactivity via the strategies of combinatorial biosynthesis.
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