کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1358475 | 981345 | 2012 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Functional characterization of recombinant hyoscyamine 6β-hydroxylase from Atropa belladonna Functional characterization of recombinant hyoscyamine 6β-hydroxylase from Atropa belladonna](/preview/png/1358475.png)
(−)-Hyoscyamine, the enantiomerically pure form of atropine, and its derivative scopolamine are tropane alkaloids that are extensively used in medicine. Hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), a monomeric α-ketoglutarate dependent dioxygenase, converts (−)-hyoscyamine to its 6,7-epoxy derivative, scopolamine, in two sequential steps. In this study, H6H of Atropa belladonna (AbH6H) was cloned, heterologously expressed in Escherichia coli, purified and characterized. The catalytic efficiency of AbH6H, especially for the second oxidation, was found to be low, and this may be one of the reasons why Atropa belladonna produces less scopolamine than other species in the same family. 6,7-Dehydrohyoscyamine, a potential precursor for the last step of epoxidation, was shown not to be an obligatory intermediate in the biosynthesis of scopolamine using purified AbH6H with an in vitro 18O labeling experiment. Moreover, the nitrogen atom in the tropane ring of (−)-hyoscyamine was found to play an important role in substrate recognition.
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Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 14, 15 July 2012, Pages 4356–4363