The biosynthesis of lipoic acid: a saga of death, destruction, and rebirth
Research in the Booker Lab focuses on understanding how Nature harnesses the power of radicals to effect kinetically challenging enzymatic reactions, many of which are critical to proper cellular functioning. Much of the lab’s work has centered around the enzymatic use of S-adenosylmethionine and iron-sulfur clusters to generate a 5’-deoxyadenosyl 5’-radical, used as a key intermediate by members of the radical S-adenosylmethionine (SAM) superfamily to catalyze over 60 different reaction types. One major interest of the Booker Lab is the use of radical SAM chemistry to catalyze the methylation of unactivated C–H bonds, reactions that are central to some mechanisms for antibiotic resistance and in the biosynthesis of numerous antibiotics, antitumor agents and other natural products that have medicinal value. A second major interest is the use of radical SAM chemistry to catalyze the attachment of sulfur atoms to unactivated carbon centers, which occurs in the biosynthesis of biotin and lipoic acid as well as in the maturation of some ribosomal proteins and hypermodified tRNAs.
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