Antibiotic optimization via in vitro glycorandomization

被引：194

作者：

Fu, X ^{[1
]}

Albermann, C ^{[1
]}

Jiang, JQ ^{[1
]}

Liao, JC ^{[1
]}

Zhang, CS ^{[1
]}

Thorson, JS ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Pharm, Lab Biosynthet Chem, Madison, WI 53705 USA

来源：

NATURE BIOTECHNOLOGY | 2003年 / 21卷 / 12期

关键词：

D O I：

10.1038/nbt909

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：

In nature, the attachment of sugars to small molecules is often used to mediate targeting, mechanism of action and/ or pharmacology. As an alternative to pathway engineering or total synthesis, we report a useful method, in vitro glycorandomization (IVG), to diversify the glycosylation patterns of complex natural products. We have used flexible glycosyltransferases on nucleotide diphosphosugar (NDP-sugar) libraries to generate glycorandomized natural products and then applied chemoselective ligation to produce monoglycosylated vancomycins that rival vancomycin.

引用

页码：1467 / 1469

页数：3

共 18 条

[1] Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala [J].

Ge, M ;

Chen, Z ;

Onishi, HR ;

Kohler, J ;

Silver, LL ;

Kerns, R ;

Fukuzawa, S ;

Thompson, C ;

Kahne, D .

SCIENCE, 1999, 284 (5413) :507-511

[2] Chemoselective approaches to glycoprotein assembly [J].

Hang, HC ;

Bertozzi, CR .

ACCOUNTS OF CHEMICAL RESEARCH, 2001, 34 (09) :727-736

[3] STERIC EFFECTS ON THE REGIOSELECTIVITY OF AN AZIDE-ALKYNE DIPOLAR CYCLOADDITION REACTION - THE SYNTHESIS OF HUMAN-LEUKOCYTE ELASTASE INHIBITORS [J].

HLASTA, DJ ;

ACKERMAN, JH .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (21) :6184-6189

[4] Vancomycin assembly: Nature's way [J].

Hubbard, BK ;

Walsh, CT .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (07) :730-765

[5]

Kolb HC, 2001, ANGEW CHEM INT EDIT, V40, P2004, DOI 10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO

[6]

2-5

[7] Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: Novel glycopeptides [J].

Losey, HC ;

Peczuh, MW ;

Chen, Z ;

Eggert, US ;

Dong, SD ;

Pelczer, I ;

Kahne, D ;

Walsh, CT .

BIOCHEMISTRY, 2001, 40 (15) :4745-4755

[8] Incorporation of glucose analogs by GtfE and GtfD from the vancomycin biosynthetic pathway to generate variant glycopeptides [J].

Losey, HC ;

Jiang, JQ ;

Biggins, JB ;

Oberthür, M ;

Ye, XY ;

Dong, SD ;

Kahne, D ;

Thorson, JS ;

Walsh, CT .

CHEMISTRY & BIOLOGY, 2002, 9 (12) :1305-1314

[9] Altering the glycosylation pattern of bioactive compounds [J].

Méndez, C ;

Salas, JA .

TRENDS IN BIOTECHNOLOGY, 2001, 19 (11) :449-456

[10]

Nicolaou KC, 1999, ANGEW CHEM INT EDIT, V38, P2096, DOI 10.1002/(SICI)1521-3773(19990802)38:15<2096::AID-ANIE2096>3.0.CO

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