Engineered production of iso-migrastatin in heterologous Streptomyces hosts

被引：46

作者：

Feng, Zhiyang ^{[1
]}

Wang, Liyan ^{[1
]}

Rajski, Scott R. ^{[1
]}

Xu, Zhinan ^{[4
]}

Coeffet-LeGal, Marie F. ^{[5
]}

Shen, Ben ^{[1
,2
,3
]}

机构：

[1] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA

[2] Univ Wisconsin, Univ Wisconsin Natl Cooperat Drug Discovery Grp, Madison, WI 53705 USA

[3] Univ Wisconsin, Dept Chem, Madison, WI 53705 USA

[4] Zhejiang Univ, Inst Bioengn, Dept Chem Engn & Bioengn, Hangzhou 310027, Zhejiang, Peoples R China

[5] Cubist Pharmaceut Inc, Lexington, MA 02421 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 06期

关键词：

CELL-MIGRATION INHIBITORS; COMPLETE GENOME SEQUENCE; NATURAL-PRODUCTS; GENE-CLUSTER; POLYKETIDE SYNTHASE; COELICOLOR A3(2); EXPRESSION; DISCOVERY; BIOSYNTHESIS; CONGENERS;

D O I：

10.1016/j.bmc.2008.10.074

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：

Glutarimide-containing polyketides such as migrastatin (MGS) are well known for their ability to inhibit tumor cell migration. We have previously shown that MGS is derived from iso-migrastatin (iso-MGS) via a H2O-mediated ring-expansion rearrangement. A bacterial artificial chromosome (BAC) library of Streptomyces platensis NRRL18993, an iso-MGS producer, was constructed. From this library, pBS11001, a BAC clone harboring the intact iso-MGS biosynthetic gene cluster, was identified. Mobilization of pBS11001 into five heterologous Streptomyces hosts afforded recombinant strains, SB11001, SB11002, SB11003, SB11004, and SB11005, respectively. Under a standard set of media and fermentation conditions, the recombinant strains all produced the same pro. le of iso-MGS as that of S. platensis NRRL18993. These findings highlight the strength and flexibility of the BAC-based technology for natural product production and engineering in heterologous Streptomyces model hosts. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2147 / 2153

页数：7

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