Unusually versatile: While the β-carbon thioether linkage in lantibiotics has long been appreciated and is relatively well characterized, a recent publication shows that the unusual sulfur-to-α-carbon thioether crosslinks in subtilosin A are produced by a radical SAM enzyme, AlbA, that contains two [4 Fe-4 S] clusters, thus highlighting the versatility of post-translational modifications in natural product biosynthesis.
[Show abstract][Hide abstract] ABSTRACT: Enzymes in the radical SAM (RS) superfamily catalyze a wide variety of reactions through unique radical chemistry. The characteristic markers of the superfamily include a [4Fe-4S] cluster coordinated to the protein via a cysteine triad motif, typically CX(3)CX(2)C, with the fourth iron coordinated by S-adenosylmethionine (SAM). The SAM serves as a precursor for a 5'-deoxyadenosyl radical, the central intermediate in nearly all RS enzymes studied to date. The SAM-bound [4Fe-4S] cluster is located within a partial or full triosephosphate isomerase (TIM) barrel where the radical chemistry occurs protected from the surroundings. In addition to the TIM barrel and a RS [4Fe-4S] cluster, many members of the superfamily contain additional domains and/or additional Fe-S clusters. Recently characterized superfamily members are providing new examples of the remarkable range of reactions that can be catalyzed, as well as new structural and mechanistic insights into these fascinating reactions.
Current Opinion in Structural Biology 11/2012; 22(6). DOI:10.1016/j.sbi.2012.10.005 · 7.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enzymes are generally believed to be highly regio- and stereo-selective catalysts that strictly control the reaction coordinates and dominate the final catalytic outcomes. However, recent studies have started to suggest that substrates sometimes play key roles in determining the product selectivity in enzyme catalysis. Here we highlighted several enzymatic reactions in natural product biosynthesis, in which the stereoselectivity is, at least in large part, governed by the intrinsic properties of the substrate rather than enzyme characteristics. Understanding the mechanism of the substrate-controlled stereospecificity may not only expand our knowledge of enzyme catalysis and enzyme evolution, but also guide bio-engineering efforts to produce novel valuable products.
ACS Chemical Biology 04/2015; 10(7). DOI:10.1021/acschembio.5b00104 · 5.33 Impact Factor
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