Elucidation of the Cryptic Methyl Group Epimerase Activity of Dehydratase Domains from Modular Polyketide Synthases Using a Tandem Modules Epimerase Assay

作者：Xie Xinqiang; Garg Ashish; Khosla Chaitan; Cane David E^*

来源：Journal of the American Chemical Society, 2017, 139(28): 9507-9510.

DOI：10.1021/jacs.7b05502

Dehydratase (DH) domains of cryptic function are often found in polyketide synthase (PKS) modules that produce epimerized (2S)-2-methyl-3-keto-acyl-ACP (acyl carrier protein) intermediates. A combination of tandem equilibrium isotope exchange (EIX) and a newly developed Tandem Modules Epimerase assay revealed the intrinsic epimerase activity of NanDH1 and NanDH5, from modules 1 and 5, respectively, of the nanchangmycin (1) PKS as well of NigDH1, from module 1 of the nigericin (3) PKS. Unexpectedly, all three epimerase-active DH domains were also found to possess intrinsic dehydratase activity, whereas the conventional DH domains, EryDH4, from module 4 of the erythromycin synthase, and NanDH2 from module 2 of the nanchangmycin synthase, were shown to have cryptic epimerase activity.

• 出版日期2017-7-19