title: Echinomycin biosynthesis.
abstract: Echinomycin is an antitumor antibiotic secondary metabolite isolated from streptomycetes, whose core structure is biosynthesized by nonribosomal peptide synthetase (NRPS). The echinomycin biosynthetic pathway was successfully reconstituted in Escherichia coli. NRPS often contains a thioesterase domain at its C terminus for cyclorelease of the elongating peptide chain. Those thioesterase domains were shown to exhibit significant substrate tolerance. More recently, an oxidoreductase Ecm17, which forms the disulfide bridge in triostin A, was characterized. Surprisingly, an unrelated disulfide-forming enzyme GliT for gliotoxin biosynthesis was also able to catalyze the same reaction, providing another example of broad substrate specificity in secondary metabolite biosynthetic enzymes. Those promiscuous catalysts can be a valuable tool in generating diversity in natural products analogs we can produce heterologously.
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Sato
authors.forename: Takehito
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Kinya
authors.initials: K
authors.lastname: Hotta
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D055162:Biocatalysis; D053898:Biosynthetic Pathways; D003500:Cyclization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004448:Echinomycin / Q000096:biosynthesis* / Q000737:chemistry; D050864:Sulfite Reductase (NADPH) / Q000378:metabolism
chemical_list: D004220:Disulfides; D004448:Echinomycin; D050864:Sulfite Reductase (NADPH)