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Mutasynthesis of Aureonitrile: An Aureothin Derivative with Significantly Improved Cytostatic Effect
Author(s) -
Ziehl Martina,
He Jing,
Dahse HansMartin,
Hertweck Christian
Publication year - 2005
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.200461990
Subject(s) - polyketide , chemistry , stereochemistry , nitrile , metabolite , derivative (finance) , polyketide synthase , enzyme , streptomyces , biochemistry , combinatorial chemistry , biology , biosynthesis , organic chemistry , bacteria , genetics , financial economics , economics
Tapping nature's biosynthetic potential : Formation of the rare p ‐nitro benzoate precursor of aureothin, a mixed polyketide metabolite of Streptomyces thioluteus , requires two key enzymes: a p ‐amino benzoate synthase and an N ‐oxygenase. Feeding of surrogates to engineered block mutants (e.g. S. lividans ZX1::pHJ97) reveals that the iterative modular aureothin polyketide also accepts p ‐cyano benzoate as the starter, which is subsequently processed to the nitrile analogue of aureothin, aureonitrile, which has improved cytostatic properties.