Application of the nucleotidylyltransferase Ep toward the chemoenzymatic synthesis of dTDP-desosamine analogues

被引:27
作者
Jiang, JQ [1 ]
Albermann, C [1 ]
Thorson, JS [1 ]
机构
[1] Univ Wisconsin, Lab Biosynthet Chem, Pharmaceut Sci Div, Sch Pharm, Madison, WI 53705 USA
关键词
antibiotics; enzyme catalysis; glycorandomization; glycosyltransferases; nucleotides;
D O I
10.1002/cbic.200200566
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
Sweet transfer: The macrolide sugar β-D-desosamine (1) is a key contributor to the anti-infective properties of many macrolide antibiotics, and methods to alter this substituent may lead to macrolide variants with enhanced properties. The application of a nucleotidylyltransferase (Ep) toward the synthesis of analogues of the precursor dTDP-desosamine is demonstrated and the substrate specificity of this important class of enzyme and its integral participation in natural product 'glycorandomization' is commented on.
引用
收藏
页码:443 / 446
页数:4
相关论文
共 34 条
[1]  
ALBERMANN C, 2003, IN PRESS ORG LETT
[2]   Expanding pyrimidine diphosphosugar libraries via structure-based nucleotidylyltransferase engineering [J].
Barton, WA ;
Biggins, JB ;
Jiang, JQ ;
Thorson, JS ;
Nikolov, DB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13397-13402
[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]  
BARTON WA, UNPUB
[5]   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
[6]  
Chang CW, 2000, ANGEW CHEM INT EDIT, V39, P2160, DOI 10.1002/1521-3773(20000616)39:12<2160::AID-ANIE2160>3.0.CO
[7]  
2-E
[8]  
CHANG CW, 2000, ANGEW CHEM, V112, P2244
[9]   Synthesis of TDP-3-amino-3,4,6-trideoxy-α-D-xylo-hexopyranose -: The immediate precursor of TDP-α-D-desosamine [J].
Chang, CWT ;
Liu, HW .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (11) :1493-1496
[10]   Expression, purification, and characterization of two N,N-dimethyltransferases, TylM1 and DesVI, involved in the biosynthesis of mycaminose and desosamine [J].
Chen, HW ;
Yamase, H ;
Murakami, K ;
Chang, CW ;
Zhao, LS ;
Zhao, ZB ;
Liu, HW .
BIOCHEMISTRY, 2002, 41 (29) :9165-9183