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Functional Characterization of MpaG′, the O‐Methyltransferase Involved in the Biosynthesis of Mycophenolic Acid
Authors:Dr Wei Zhang  Shaona Cao  Dr Li Qiu  Dr Fengxia Qi  Zhong Li  Ying Yang  Dr Shaohua Huang  Fali Bai  Prof Dr Changning Liu  Prof Dr Xiaobo Wan  Prof Dr Shengying Li
Affiliation:1. Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao, Shandong 266101 (China);2. Key Laboratory of Bio‐based Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, No. 189 Songling Road, Qingdao, Shandong 266101 (China);3. University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049 (China);4. Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Yunnan 666303 (China)
Abstract: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.
Keywords:biosynthesis  methyltransferases  mycophenolic acid  substrate flexibility  transferases
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