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Characterization of the Actinonin Biosynthetic Gene Cluster
Author(s) -
Wolf Felix,
Leipoldt Franziska,
Kulik Andreas,
Wibberg Daniel,
Kalinowski Jörn,
Kaysser Leonard
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800116
Subject(s) - gene cluster , biosynthesis , hydroxylation , nonribosomal peptide , heterologous expression , biochemistry , chemistry , gene , enzyme , moiety , natural product , biology , stereochemistry , recombinant dna
The hydroxamate moiety of the natural product actinonin mediates inhibition of metalloproteinases because of its chelating properties towards divalent cations in the active site of those enzymes. Owing to its antimicrobial activity, actinonin has served as a lead compound for the development of new antibiotic drug candidates. Recently, we identified a putative gene cluster for the biosynthesis of actinonin. Here, we confirm and characterize this cluster by heterologous pathway expression and gene‐deletion experiments. We assigned the biosynthetic gene cluster to actinonin production and determine the cluster boundaries. Furthermore, we establish that ActI, an AurF‐like oxygenase, is responsible for the N‐hydroxylation reaction that forms the hydroxamate warhead. Our findings provide the basis for more detailed investigations of actinonin biosynthesis.