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Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase
Journal of Natural Medicines ( IF 3.3 ) Pub Date : 2022-06-29 , DOI: 10.1007/s11418-022-01635-0
Sherif Ahmed Hamdy 1, 2 , Takeshi Kodama 2 , Yu Nakashima 2 , Xiaojie Han 2 , Takashi Matsui 3, 4 , Hiroyuki Morita 2
Affiliation  

CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a β-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the “regular-type” dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His6-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.



中文翻译:

真菌吲哚异戊二烯转移酶酶促形成异戊二烯β-咔啉

来自烟曲霉的CdpNPT是一种真菌吲哚异戊二烯转移酶 (IPT),具有显着的底物混杂性以产生异戊二烯化化合物。我们对 CdpNPT 对β-咔啉、harmol ( 1 ) 的催化潜力的首次研究表明,该酶还接受1作为异戊二烯受体,二甲基烯丙基二磷酸 (DMAPP) 作为异戊二烯供体并选择性异戊二烯化的 C-6 位置1通过“常规型”二甲基烯丙基化生成 6-(3-二甲基烯丙基)harmol ( 2 )。此外,我们对与1复合的 C-His 6标记的​​ CdpNPT (38-440) 截短突变体的 X 射线晶体结构分析DMAPP 与 CdpNPT (38-440) 突变体晶体结构的对接研究表明,CdpNPT 可以采用两步异戊二烯化系统生产2

更新日期:2022-06-29
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