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Nat Chem Biol. 2012 Feb 26;8(4):350-7. doi: 10.1038/nchembio.798.

The radical SAM enzyme AlbA catalyzes thioether bond formation in subtilosin A.

Author information

1
Department of Chemistry-Biochemistry, Philipps-Universität Marburg, Marburg, Germany.

Erratum in

  • Nat Chem Biol. 2012 Aug;8(8):737.

Abstract

Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalanines, respectively. In this study, we demonstrate that these bonds are synthesized by the radical S-adenosylmethionine enzyme AlbA, which is encoded by the sbo-alb operon and comprises two [4Fe-4S] clusters. One [4Fe-4S] cluster is coordinated by the prototypical CXXXCXXC motif and is responsible for the observed S-adenosylmethionine cleavage reaction, whereas the second [4Fe-4S] cluster is required for the generation of all three thioether linkages. On the basis of the obtained results, we propose a new radical mechanism for thioether bond formation. In addition, we show that AlbA-directed substrate transformation is leader-peptide dependent, suggesting that thioether bond formation is the first step during subtilosin A maturation.

PMID:
22366720
DOI:
10.1038/nchembio.798
[Indexed for MEDLINE]

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