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Functional Characterization of MpaG′, the O‐Methyltransferase Involved in the Biosynthesis of Mycophenolic Acid
Author(s) -
Zhang Wei,
Cao Shaona,
Qiu Li,
Qi Fengxia,
Li Zhong,
Yang Ying,
Huang Shaohua,
Bai Fali,
Liu Changning,
Wan Xiaobo,
Li Shengying
Publication year - 2015
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.201402600
Subject(s) - methyltransferase , mycophenolic acid , biosynthesis , methylation , o methyltransferase , gene cluster , chemistry , biochemistry , methionine , gene , in vitro , mycophenolate , substrate (aquarium) , stereochemistry , biology , amino acid , medicine , transplantation , surgery , ecology
Mycophenolic acid (MPA, 1 ) is a clinically important immunosuppressant. In this report, a gene cluster mpa′ responsible for the biosynthesis of 1 was identified from Penicillium brevicompactum NRRL 864. The S ‐adenosyl‐ L ‐methionine‐dependent (SAM‐dependent) O‐methyltransferase encoded by the mpaG′ gene was functionally and kinetically characterized in vitro. MpaG′ catalyzes the methylation of demethylmycophenolic acid (DMMPA, 6 ) to form 1 . It also showed significant substrate flexibility by methylating two structural derivatives of 6 prepared by organic synthesis.