ISSN:
0894-3230
Keywords:
biotin
;
in vivo C - S bond formation
;
radical chemistry
;
reducing conditions
;
Chemistry
;
Theoretical, Physical and Computational Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Physics
Notes:
The last step in the biosynthesis of biotin involves the formation of carbon-sulfur bonds at non-activated carbons catalyzed by biotin synthase. S-Adenosylmethionine (AdoMet) and an electron source are essential for activity in cell-free systems. This important finding connects biotin synthase to a family of enzymes, namely pyruvate-formate lyase, anaerobic ribonucleotide reductase and lysine 2,3-aminomutase, which use the same cofactors. Additional experimental data led to the proposition of the following general mechanism. The carbons to be functionalized are first activated by homolytic cleavage of the C - H bonds, initiated by the deoxyadenosyl radical produced by a monoelectronic reductive cleavage of AdoMet with NADPH as electron source. The electron transfer system involves flavoproteins and very likely the [Fe - S] center of biotin synthase. NADPH and the flavoproteins can be replaced by photoreduced deazaflavin. By using a deuterated substrate, a deuterium transfer into deoxyadenosine has been observed, indicating that biotin synthase should be closely related to lysine 2,3-aminomutase, which uses AdoMet as a surrogate of vitamin B12. The source of sulfur, the nature of the immediate sulfur donor and hence the mechanism of trapping of the intermediate radicals are still unknown. © 1998 John Wiley & Sons, Ltd.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
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