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Catalysis of Extracellular Deamination by a FAD‐Linked Oxidoreductase after Prodrug Maturation in the Biosynthesis of Saframycin A
Author(s) -
Song LiQiang,
Zhang YingYing,
Pu JinYue,
Tang ManCheng,
Peng Chao,
Tang GongLi
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201704726
Subject(s) - deamination , biosynthesis , oxidative deamination , oxidoreductase , chemistry , biochemistry , stereochemistry , enzyme
The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM‐A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however, the follow‐up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane‐bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase covalently associated with FAD, subsequently performs an oxidative deamination extracellularly. These results not only fill in the missing steps of SFM‐A biosynthesis, but also reveal that a FAD‐binding oxidoreductase catalyzes an unexpected deamination reaction through an unconventional extracellular pathway in Streptmyces bacteria.