In vivo formation of C—S bonds in biotin. An example of radical chemistry under reducing conditions
✍ Scribed by A. Marquet; D. Florentin; O. Ploux; B. Tse Sum Bui
- Book ID
- 101287203
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 191 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0894-3230
No coin nor oath required. For personal study only.
✦ Synopsis
The last step in the biosynthesis of biotin involves the formation of carbon-sulfur bonds at nonactivated 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.