Unusual sugar biosynthesis and natural product glycodiversification

被引:281
作者
Thibodeaux, Christopher J.
Melancon, Charles E.
Liu, Hung-wen
机构
[1] Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA
[2] Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA
[3] Univ Texas, Coll Pharm, Div Med Chem, Austin, TX 78712 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature05814
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The enzymes involved in the biosynthesis of carbohydrates and the attachment of sugar units to biological acceptor molecules catalyse an array of chemical transformations and coupling reactions. In prokaryotes, both common sugar precursors and their enzymatically modified derivatives often become substituents of biologically active natural products through the action of glycosyltransferases. Recently, researchers have begun to harness the power of these biological catalysts to alter the sugar structures and glycosylation patterns of natural products both in vivo and in vitro. Biochemical and structural studies of sugar biosynthetic enzymes and glycosyltransferases, coupled with advances in bioengineering methodology, have ushered in a new era of drug development.
引用
收藏
页码:1008 / 1016
页数:9
相关论文
共 98 条
[1]   High-throughput screening methodology for the directed evolution of glycosyltransferases [J].
Aharoni, Amir ;
Thieme, Karena ;
Chiu, Cecilia P. C. ;
Buchini, Sabrina ;
Lairson, Luke L. ;
Chen, Hongming ;
Strynadka, Natalie C. J. ;
Wakarchuk, Warren W. ;
Withers, Stephen G. .
NATURE METHODS, 2006, 3 (08) :609-614
[2]   Substrate specificity of NovM: Implications for novobiocin biosynthesis and glycorandomization [J].
Albermann, C ;
Soriano, A ;
Jiang, JQ ;
Vollmer, H ;
Biggins, JB ;
Barton, WA ;
Lesniak, J ;
Nikolov, DB ;
Thorson, JS .
ORGANIC LETTERS, 2003, 5 (06) :933-936
[3]   Structure, mechanism and engineering of a nucleotidylyltransferase as a first step toward glycorandomization [J].
Barton, WA ;
Lesniak, J ;
Biggins, JB ;
Jeffrey, PD ;
Jiang, JQ ;
Rajashankar, KR ;
Thorson, JS ;
Nikolov, DB .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (06) :545-551
[4]   The hedamycin locus implicates a novel aromatic PKS priming mechanism [J].
Bililign, T ;
Hyun, CG ;
Williams, JS ;
Czisny, AM ;
Thorson, JS .
CHEMISTRY & BIOLOGY, 2004, 11 (07) :959-969
[5]   Structure of UDP complex of UDP-galactose:β-galactoside-α-1,3-galactosyltransferase at 1.53-Å resolution reveals a conformational change in the catalytically important C terminus [J].
Boix, E ;
Swaminathan, GJ ;
Zhang, YN ;
Natesh, R ;
Brew, K ;
Acharya, KR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48608-48614
[6]   Structural basis of ordered binding of donor and acceptor substrates to the retaining glycosyltransferase, α-1,3-galactosyltransferase [J].
Boix, E ;
Zhang, YN ;
Swaminathan, GJ ;
Brew, K ;
Acharya, KR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (31) :28310-28318
[7]   Biosynthesis of desosamine: Construction of a new macrolide carrying a genetically designed sugar moiety [J].
Borisova, SA ;
Zhao, LS ;
Sherman, DH ;
Liu, HW .
ORGANIC LETTERS, 1999, 1 (01) :133-136
[8]   Substrate Specificity of the Macrolide-Glycosylating Enzyme Pair DesVII/DesVIII: Opportunities, Limitations, and Mechanistic Hypotheses [J].
Borisova, SA ;
Zhang, CS ;
Takahashi, H ;
Zhang, H ;
Wong, AW ;
Thorson, JS ;
Liu, HW .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (17) :2748-2753
[9]   Glycoside hydrolases and glycosyltransferases: families and functional modules [J].
Bourne, Y ;
Henrissat, B .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2001, 11 (05) :593-600
[10]   Structural and functional features of glycosyltransferases [J].
Breton, C ;
Mucha, J ;
Jeanneau, C .
BIOCHIMIE, 2001, 83 (08) :713-718