The in vitro characterization of the iterative avermectin glycosyltransferase AveBI reveals reaction reversibility and sugar nucleotide flexibility.
The glycosyltransferase AveBI, which is involved in the biosynthesis of the macrolide antihelmintic avermectin (AVM), was characterized in vitro. AveBI was confirmed to catalyze two separate iterative additions of l-oleandrose, and the reversibility of AveBI-catalyzed reaction was also demonstrated. Investigation of sugar nucleotide specificity revealed 10 unique sugar nucleotide substrates which, in combination with five distinct aglycones, led to the production of 50 differentially glycosylated AVM variants.
Zhang
Changsheng
C
Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, National Cooperative Drug Discovery Program, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
Albermann
Christoph
C
Fu
Xun
X
Thorson
Jon S
JS
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D016695:Glycosyltransferases / Q000737:chemistry*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D009711:Nucleotides / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D009711:Nucleotides; D007559:Ivermectin; C019264:avermectin; D016695:Glycosyltransferases