Identification of the gene cluster involved in muraymycin biosynthesis from Streptomyces sp NRRL 30471

被引：46

作者：

Cheng, Lin ^{[1
,2
]}

Chen, Wenqing ^{[1
,2
,3
]}

Zhai, Lipeng ^{[1
,2
]}

Xu, Dongmei ^{[1
,2
]}

Huang, Tingting ^{[1
,2
]}

Lin, Shuangjun ^{[1
,2
]}

Zhou, Xiufen ^{[1
,2
]}

Deng, Zixin ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Lab Microbial Metab, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai 200030, Peoples R China

[3] Wuhan Univ, Coll Pharm, Wuhan 430072, Peoples R China

来源：

MOLECULAR BIOSYSTEMS | 2011年 / 7卷 / 03期

基金：

美国国家科学基金会;

关键词：

VIOMYCIN BIOSYNTHESIS; ASYMMETRIC-SYNTHESIS; COELICOLOR A3(2); GENOME SEQUENCE; ANTIBIOTICS; PROTEIN; INHIBITORS; PATHWAY; DNA;

D O I：

10.1039/c0mb00237b

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：920 / 927

页数：8

共 30 条

[1] BASIC LOCAL ALIGNMENT SEARCH TOOL [J].

ALTSCHUL, SF ;

GISH, W ;

MILLER, W ;

MYERS, EW ;

LIPMAN, DJ .

JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410

[2]

[Anonymous], 1989, Molecular Cloning: A Laboratory

[3] Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2) [J].

Bentley, SD ;

Chater, KF ;

Cerdeño-Tárraga, AM ;

Challis, GL ;

Thomson, NR ;

James, KD ;

Harris, DE ;

Quail, MA ;

Kieser, H ;

Harper, D ;

Bateman, A ;

Brown, S ;

Chandra, G ;

Chen, CW ;

Collins, M ;

Cronin, A ;

Fraser, A ;

Goble, A ;

Hidalgo, J ;

Hornsby, T ;

Howarth, S ;

Huang, CH ;

Kieser, T ;

Larke, L ;

Murphy, L ;

Oliver, K ;

O'Neil, S ;

Rabbinowitsch, E ;

Rajandream, MA ;

Rutherford, K ;

Rutter, S ;

Seeger, K ;

Saunders, D ;

Sharp, S ;

Squares, R ;

Squares, S ;

Taylor, K ;

Warren, T ;

Wietzorrek, A ;

Woodward, J ;

Barrell, BG ;

Parkhill, J ;

Hopwood, DA .

NATURE, 2002, 417 (6885) :141-147

[4] PLASMID CLONING VECTORS FOR THE CONJUGAL TRANSFER OF DNA FROM ESCHERICHIA-COLI TO STREPTOMYCES SPP [J].

BIERMAN, M ;

LOGAN, R ;

OBRIEN, K ;

SENO, ET ;

RAO, RN ;

SCHONER, BE .

GENE, 1992, 116 (01) :43-49

[5] Characterization of the Polyoxin Biosynthetic Gene Cluster from Streptomyces cacaoi and Engineered Production of Polyoxin H [J].

Chen, Wenqing ;

Huang, Tingting ;

He, Xinyi ;

Meng, Qingqing ;

You, Delin ;

Bai, Linquan ;

Li, Jialiang ;

Wu, Mingxuan ;

Li, Rui ;

Xie, Zhoujie ;

Zhou, Huchen ;

Zhou, Xiufen ;

Tan, Huarong ;

Deng, Zixin .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (16) :10627-10638

[6] Asymmetric synthesis of (2S,3R)-capreomycidine and the total synthesis of capreomycin IB [J].

DeMong, DE ;

Williams, RM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (28) :8561-8565

[7]

Funabashi M, 2010, NAT CHEM BIOL, V6, P581, DOI [10.1038/NCHEMBIO.393, 10.1038/nchembio.393]

[8] PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin [J].

Gust, B ;

Challis, GL ;

Fowler, K ;

Kieser, T ;

Chater, KF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (04) :1541-1546

[9] FramePlot: a new implementation of the Frame analysis for predicting protein-coding regions in bacterial DNA with a high G plus C content [J].

Ishikawa, J ;

Hotta, K .

FEMS MICROBIOLOGY LETTERS, 1999, 174 (02) :251-253

[10] A biosynthetic gene cluster for the acetyl-CoA carboxylase inhibitor andrimid [J].

Jin, Mi ;

Fischbach, Michael A. ;

Clardy, Jon .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (33) :10660-10661

← 1 2 3 →