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

共 44 条

[31] Artificial chromosomes for antibiotic-producing actinomycetes [J].

Sosio, M ;

Giusino, F ;

Cappellano, C ;

Bossi, E ;

Puglia, AM ;

Donadio, S .

NATURE BIOTECHNOLOGY, 2000, 18 (03) :343-345

[32] Cloning and heterologous expression of the epothilone gene cluster [J].

Tang, L ;

Shah, S ;

Chung, L ;

Carney, J ;

Katz, L ;

Khosla, C ;

Julien, B .

SCIENCE, 2000, 287 (5453) :640-642

[33]

Thomas MG, 2005, ANTICANCER AGENTS FROM NATURAL PRODUCTS, P519

[34]

Van Lanen SG, 2008, CURR OPIN DRUG DISC, V11, P186

[35] Microbial genomics for the improvement of natural product discovery [J].

Van Lanen, Steven G. ;

Shen, Ben .

CURRENT OPINION IN MICROBIOLOGY, 2006, 9 (03) :252-260

[36]

VANLANEN S, 2006, DRUG DISCOV TODAY, V1, P409

[37] Heterologous expression of a myxobacterial natural products assembly line in pseudomonads via red/ET recombineering [J].

Wenzel, SC ;

Gross, F ;

Zhang, YM ;

Fu, J ;

Stewart, AF ;

Müller, R .

CHEMISTRY & BIOLOGY, 2005, 12 (03) :349-356

[38] Recent developments towards the heterologous expression of complex bacterial natural product biosynthetic pathways [J].

Wenzel, SC ;

Müller, R .

CURRENT OPINION IN BIOTECHNOLOGY, 2005, 16 (06) :594-606

[39] Migrastatin and a new compound, isomigrastatin, from Streptomyces platensis [J].

Woo, EJ ;

Starks, CM ;

Carney, JR ;

Arslanian, R ;

Cadapan, L ;

Zavala, S ;

Licari, P .

JOURNAL OF ANTIBIOTICS, 2002, 55 (02) :141-146

[40]

Woodhouse EC, 1997, CANCER-AM CANCER SOC, V80, P1529, DOI 10.1002/(SICI)1097-0142(19971015)80:8+<1529::AID-CNCR2>3.3.CO

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