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Enzymatic cascade reactions in biosynthesis

TitleEnzymatic cascade reactions in biosynthesis
Publication TypeJournal Article
Year of Publication2019
AuthorsWalsh CT, Moore BS
Date Published2019/05
Type of ArticleReview
ISBN Number1433-7851
Accession NumberWOS:000476423300004
Keywordsatom economy; catalytic; chemistry; cope; coupling reaction; crystal-structure; diels-alderase; electrophilic cascades; gene-cluster; gibberellin biosynthesis; mechanism; natural products; nucleophilic cascades; oxidative cyclization; pericyclic cascades; radical cascades; rearrangement; reductive cyclization

Enzyme-mediated cascade reactions are widespread in biosynthesis. To facilitate comparison with the mechanistic categorizations of cascade reactions by synthetic chemists and delineate the common underlying chemistry, we discuss four types of enzymatic cascade reactions: those involving nucleophilic, electrophilic, pericyclic, and radical reactions. Two subtypes of enzymes that generate radical cascades exist at opposite ends of the oxygen abundance spectrum. Iron-based enzymes use O-2 to generate high valent iron-oxo species to homolyze unactivated C-H bonds in substrates to initiate skeletal rearrangements. At anaerobic end, enzymes reversibly cleave S-adenosylmethionine (SAM) to generate the 5 '-deoxyadenosyl radical as a powerful oxidant to initiate C-H bond homolysis in bound substrates. The latter enzymes are termed radical SAM enzymes. We categorize the former as thwarted oxygenases.

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