title: Epidithiodiketopiperazine biosynthesis: a four-enzyme cascade converts glutathione conjugates into transannular disulfide bridges.
abstract: Enzyme quartet: Isolation of the first sulfur-bearing intermediate of the gliotoxin pathway in Aspergillus fumigatus and successful in vitro conversion of the bisglutathione adduct into an intact epidithiodiketopiperazine by a four-enzyme cascade (including glutamyltransferase GliK and dipeptidase GliJ) revealed an outstanding adaptation of a primary metabolic pathway into natural product biosynthesis that is widespread in fungi.
authors.affiliation: Depts. of Molecular and Applied Microbiology, Biomolecular Chemistry, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany).
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Scharf
authors.forename: Pranatchareeya
authors.initials: P
authors.lastname: Chankhamjon
authors.forename: Kirstin
authors.initials: K
authors.lastname: Scherlach
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heinekamp
authors.forename: Karsten
authors.initials: K
authors.lastname: Willing
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology / Q000378:metabolism*; D004150:Dipeptidases / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D005912:Gliotoxin / Q000096:biosynthesis / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism*; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004220:Disulfides; D010879:Piperazines; C583251:epidithiodiketopiperazine; D005912:Gliotoxin; D004150:Dipeptidases; C038937:dipeptidase; D005978:Glutathione
keywords: Aspergillus fumigatus; biosynthesis; dipeptidase; gliotoxin; mycotoxins