Efficient chemoenzymatic synthesis of ADP-D-glycero-beta-D-manno-heptose and a mechanistic study of ADP-L-glycero-D-manno-heptose 6-epimerase.
[reaction: see text] A chemoenzymatic synthesis of ADP-D-glycero-beta-D-manno-heptose (ADP-D,D-Hep) is described in which D,D-Hep 7-phosphate is converted to ADP-D,D-Hep by two biosynthetic enzymes. This strategy allows access to the 6''-deuterated analogue, which upon incubation with the epimerase showed complete retention of the isotopic label at the 6''-position. This provides evidence for a direct oxidation mechanism in which the hydride initially transferred to the NADP+ cofactor is subsequently returned to the same carbon in a nonstereospecific manner.
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Jay A
JA
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
Ahmed
Raef A
RA
Tanner
Martin E
ME
D000247:Adenosine Diphosphate Sugars / Q000138:chemical synthesis*; D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D000247:Adenosine Diphosphate Sugars; D010710:Phosphates; D009249:NADP; C031557:adenosine 5'-diphosphate-glycero-mannoheptose; C037213:ADP-L-glycero-D-mannoheptose-6-epimerase; D002238:Carbohydrate Epimerases