Enzymatic Pyran Formation Involved in Xiamenmycin Biosynthesis
Enzymatic Pyran Formation Involved in Xiamenmycin Biosynthesis
复制标题
厦门霉素生物合成中酶促吡喃的形成
DOI：
10.1021/acscatal.9b01034
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发表时间：
2019-06-01
期刊：
影响因子：
12.9
通讯作者：
Xu, Min Juan
中科院分区：
文献类型：
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作者：
He, Bei-Bei;Zhou, Ting;Xu, Min Juan
吡喃环是广泛存在于植物、细菌和真菌中的许多天然生物活性分子的非常常见的结构单元。然而，许多这些含吡喃分子形成的酶促过程尚不清楚。在此，我们报告的建设的吡喃环催化的合作黄素依赖性单加氧酶，XimD，和SnoaL样环化酶，XimE，在厦门霉素的生物合成。XimD催化环氧化物中间体的形成，该中间体在体外自发转化为呋喃和吡喃产物（43：1）。然后XimE催化从环氧化物形成6-内构型的吡喃环，得到苯并吡喃，厦门霉素B。此外，我们获得了XimE的晶体结构，有和没有产品，这表明一个协同机制，其中一组四个残基（Y 46-Y 90-H102-E136）合作作为一般的酸和碱。随后的结构为基础的分析可能可行的基板表明，这两个X…
The pyran ring is a very common structural unit of many natural, bioactive molecules that are widely found in plants, bacteria, and fungi. However, the enzymatic processes by which many of these pyran-containing molecules are formed are unclear. Herein, we report the construction of the pyran ring catalyzed by the cooperation of a flavin-dependent monooxygenase, XimD, and a SnoaL-like cyclase, XimE, in the biosynthesis of xiamenmycins. XimD catalyzes the formation of an epoxide intermediate that spontaneously transforms to furan and pyran products (43:1) in vitro. XimE then catalyzes the formation of the pyran ring in a 6-endo configuration from the epoxide to yield a benzopyran, xiamenmycin B. Further, we obtained the crystallographic structure of XimE, with and without product, which suggests a synergistic mechanism in which a group of four residues (Y46–Y90–H102–E136) acts cooperatively as the general acid and base. Subsequent structure-based analysis of possible viable substrates indicates that both X...