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Elucidation of Oxygenation Steps during Oviedomycin Biosynthesis and Generation of Derivatives with Increased Antitumor Activity
Author(s) -
Lombó Felipe,
Abdelfattah Mohamed S.,
Braña Alfredo F.,
Salas José A.,
Rohr Jürgen,
Méndez Carmen
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800425
Subject(s) - dehydratase , gene cluster , biosynthesis , oxygenase , polyketide , polyketide synthase , streptomyces albus , biochemistry , streptomyces , streptomycetaceae , atp synthase , chemistry , gene , biology , stereochemistry , actinomycetales , genetics , bacteria
Abstract Eight different angucyclinones have been produced in Streptomyces albus by combining three oxygenase genes together with the polyketide synthase and cyclases genes from the oviedomycin biosynthetic gene cluster from Streptomyces antibioticus ATCC 11891. Four of these compounds were fully characterized for the first time. Three of these angucyclinones—prejadomycin‐2‐carboxylate ( 2 ), 4a,12b‐dehydro‐UWM6 ( 5 ), and prejadomycin ( 3 )—show a significant increase in their in vitro antitumor activity relative to oviedomycin ( 1 ). A hypothesis for the sequence of tailoring events catalyzed by these three oxygenases during oviedomycin biosynthesis is proposed. In this hypothesis OvmOII acts as a bifunctional oxygenase/dehydratase.