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

被引：32

作者：

Funabashi, Masanori ^{[1
]}

Nonaka, Koichi ^{[1
]}

Yada, Chieko ^{[1
]}

Hosobuchi, Masahiko ^{[1
]}

Masuda, Nobuhisa ^{[2
]}

Shibata, Tomoyuki ^{[3
]}

Van Lanen, Steven G. ^{[4
]}

机构：

[1] Daiichi Sankyo Co Ltd, Proc Technol Res Labs, Pharmaceut Technol Div, Bioengn Res Grp 1, Iwaki, Fukushima 9718183, Japan

[2] Daiichi Sankyo Co Ltd, Div Res & Dev, Biol Res Labs 4, Grp 4, Tokyo, Japan

[3] Daiichi Sankyo Co Ltd, Div Res & Dev, Exploratory Res Labs 1, Grp 5, Tokyo, Japan

[4] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY USA

来源：

JOURNAL OF ANTIBIOTICS | 2009年 / 62卷 / 06期

关键词：

A-500359s; biosynthetic gene cluster; resistance gene; RT-PCR; Streptomyces griseus; TRANSLOCASE-I INHIBITORS; BLASTICIDIN-S; CLONING; ANTIBIOTICS; MILDIOMYCIN; EXPRESSION; SEQUENCE; STEPS;

D O I：

10.1038/ja.2009.38

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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. The Journal of Antibiotics (2009) 62, 325-332; doi: 10.1038/ja.2009.38; published online 29 May 2009

引用

页码：325 / 332

页数：8

共 28 条

[1]

[Anonymous], 2012, Molecular Cloning: A Laboratory Manual

[2] Cloning and heterologous expression of the entire set of structural genes for nikkomycin synthesis from Streptomyces tendae Tu901 in Streptomyces lividans [J].