Functional characterization of MpaG′, the O-methyltransferase involved in the biosynthesis of mycophenolic acid
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.
Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment
Mycophenolic acid (MPA), an inhibitor of IMP-dehydrogenase (IMPDH), is used worldwide in transplantation. Recently, numerous studies showed its importance in cancer treatment. Consequently, MPA entered clinical trials in advanced multiple myeloma patients
Chen, Liqiang,Wilson, Daniel,Jayaram, Hiremagalur N.,Pankiewicz, Krzysztof W.
p. 6685 - 6691
(2008/09/18)
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