Erythromycin biosynthesis. The 4-pro-S hydride of NADPH is utilized for ketoreduction by both module 5 and module 6 of the 6-deoxyerythronolide B synthase.
Incubation of chirally deuterated NADPH with 6-deoxyerythronolide B synthase (DEBS) modules 5 and module 6 and analysis of the derived triketide lactones established that the two ketoreductase domains, KR5 and KR6, are both specific for the 4-pro-S hydride of the nicotinamide cofactor.
Yin
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Y
Department of Chemistry, Box H, Brown University, Providence, RI 02912-9108, USA.
Gokhale
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R
Khosla
C
C
Cane
D E
DE
D001419:Bacteria / Q000201:enzymology / Q000378:metabolism; D020134:Catalytic Domain; D003903:Deuterium; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D009097:Multienzyme Complexes; C034277:6-deoxyerythronolide B; D009249:NADP; D004917:Erythromycin; D003903:Deuterium