Premium
Flavoenzyme‐Catalyzed Formation of Disulfide Bonds in Natural Products
Author(s) -
Scharf Daniel H.,
Groll Michael,
Habel Andreas,
Heinekamp Thorsten,
Hertweck Christian,
Brakhage Axel A.,
Huber Eva M.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201309302
Subject(s) - moiety , disulfide bond , chemistry , substrate (aquarium) , gliotoxin , stereochemistry , mutagenesis , combinatorial chemistry , enzyme , catalysis , biochemistry , biology , mutant , microbiology and biotechnology , aspergillus fumigatus , gene , ecology
Nature provides a rich source of compounds with diverse chemical structures and biological activities, among them, sulfur‐containing metabolites from bacteria and fungi. Some of these compounds bear a disulfide moiety that is indispensable for their bioactivity. Specialized oxidoreductases such as GliT, HlmI, and DepH catalyze the formation of this disulfide bridge in the virulence factor gliotoxin, the antibiotic holomycin, and the anticancer drug romidepsin, respectively. We have examined all three enzymes by X‐ray crystallography and activity assays. Despite their differently sized substrate binding clefts and hence, their diverse substrate preferences, a unifying reaction mechanism is proposed based on the obtained crystal structures and further supported by mutagenesis experiments.