Identification of the biosynthetic gene cluster of A-500359s in Streptomyces griseus SANK60196

A-500359s, produced by Streptomyces griseus SANK60196, are inhibitors of bacterial phospho- N -acetylmuramyl-pentapeptide translocase. They are composed of three distinct moieties: a 5′-carbamoyl uridine, an unsaturated hexuronic acid and an aminocaprolactam. Two contiguous cosmids covering a 65-kb...

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Bibliographic Details
Published in:	Journal of antibiotics Vol. 62; no. 6; pp. 325 - 332
Main Authors:	Funabashi, Masanori, Nonaka, Koichi, Yada, Chieko, Hosobuchi, Masahiko, Masuda, Nobuhisa, Shibata, Tomoyuki, Van Lanen, Steven G
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-06-2009 Nature Publishing Group
Subjects:	Anti-Bacterial Agents - biosynthesis Anti-Bacterial Agents - pharmacology Azepines - pharmacology Bacteriology Biomedical and Life Sciences Bioorganic Chemistry Biosynthesis DNA, Bacterial - biosynthesis DNA, Bacterial - genetics Drug Resistance, Bacterial - genetics E coli Escherichia coli - drug effects Escherichia coli - genetics Gene Library Genes, Bacterial - genetics Genetic Vectors Life Sciences Medicinal Chemistry Microbiology Multigene Family Open Reading Frames Organic Chemistry original-article Reverse Transcriptase Polymerase Chain Reaction Streptomyces griseus - genetics Uridine - analogs & derivatives Uridine - biosynthesis Uridine - pharmacology A-500359s biosynthetic gene cluster resistance gene RT-PCR
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Summary:	A-500359s, produced by Streptomyces griseus SANK60196, are inhibitors of bacterial phospho- N -acetylmuramyl-pentapeptide translocase. They are composed of three distinct moieties: a 5′-carbamoyl uridine, an unsaturated hexuronic acid and an aminocaprolactam. Two contiguous cosmids covering a 65-kb region of DNA and encoding 38 open reading frames (ORFs) putatively involved in the biosynthesis of A-500359s were identified. Reverse transcriptase PCR showed that most of the 38 ORFs are highly expressed during A-500359s production, but mutants that do not produce A-500359s did not express these same ORFs. Furthermore, orf21 , encoding a putative aminoglycoside 3′-phosphotransferase, was heterologously expressed in Escherichia coli and Streptomyces albus , yielding strains having selective resistance against A-500359B, suggesting that ORF21 phosphorylates the unsaturated hexuronic acid as a mechanism of self-resistance to A-500359s. In total, the data suggest that the cloned region is involved in the resistance, regulation and biosynthesis of A-500359s.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-8820 1881-1469
DOI:	10.1038/ja.2009.38