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Structural basis for the erythro ‐stereospecificity of the l ‐arginine oxygenase VioC in viomycin biosynthesis
Author(s) -
Helmetag Verena,
Samel Stefan A.,
Thomas Michael G.,
Marahiel Mohamed A.,
Essen LarsOliver
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07085.x
Subject(s) - stereochemistry , oxygenase , viomycin , chemistry , biosynthesis , hydroxylation , stereospecificity , arginine , diastereomer , biochemistry , enzyme , amino acid , catalysis , streptomycin , antibiotics
The nonheme iron oxygenase VioC from Streptomyces vinaceus catalyzes Fe(II)‐dependent and α‐ketoglutarate‐dependent Cβ‐hydroxylation of l ‐arginine during the biosynthesis of the tuberactinomycin antibiotic viomycin. Crystal structures of VioC were determined in complexes with the cofactor Fe(II), the substrate l ‐arginine, the product (2 S ,3 S )‐hydroxyarginine and the coproduct succinate at 1.1–1.3 Å resolution. The overall structure reveals a β‐helix core fold with two additional helical subdomains that are common to nonheme iron oxygenases of the clavaminic acid synthase‐like superfamily. In contrast to other clavaminic acid synthase‐like oxygenases, which catalyze the formation of threo diastereomers, VioC produces the erythro diastereomer of Cβ‐hydroxylated l ‐arginine. This unexpected stereospecificity is caused by conformational control of the bound substrate, which enforces a gauche (–) conformer for χ 1 instead of the trans conformers observed for the asparagine oxygenase AsnO and other members of the clavaminic acid synthase‐like superfamily. Additionally, the substrate specificity of VioC was investigated. The side chain of the l ‐arginine substrate projects outwards from the active site by undergoing interactions mainly with the C‐terminal helical subdomain. Accordingly, VioC exerts broadened substrate specificity by accepting the analogs l ‐homoarginine and l ‐canavanine for Cβ‐hydroxylation.