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The Thioesterase of the Erythromycin‐Producing Polyketide Synthase: Influence of Acyl Chain Structure on the Mode of Release of Substrate Analogues from the Acyl Enzyme Intermediates
Author(s) -
Weissman Kira J.,
Smith Cameron J.,
Hanefeld Ulf,
Aggarwal Ranjana,
Bycroft Matthew,
Staunton James,
Leadlay Peter F.
Publication year - 1998
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/(sici)1521-3773(19980605)37:10<1437::aid-anie1437>3.0.co;2-7
Subject(s) - thioesterase , polyketide , polyketide synthase , enzyme , chemistry , stereochemistry , substrate (aquarium) , acyl carrier protein , biochemistry , atp synthase , biosynthesis , combinatorial chemistry , biology , ecology
The production of genetically engineered polyketides depends critically on thioesterase activity for product release. In vitro studies with the thioesterase from the erythromycin polyketide synthase (PKS) have demonstrated that the ability of this enzyme to act as a universal decoupler is limited, but stereochemical variation is readily tolerated. Synthetic analogues with all four stereochemical configurations of the natural substrate's 2‐methyl‐3‐hydroxy substitution pattern ( 1 – 4 ; X= p ‐nitrophenoxy) were substrates for the enzyme.