Exploring biosynthetic diversity with trichodiene synthase.
Exploring biosynthetic diversity with trichodiene synthase.
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DOI：
10.1016/j.abb.2007.06.016
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发表时间：
2007-10
影响因子：
3.9
通讯作者：
L. Vedula;Yuxin Zhao;R. Coates;T. Koyama;D. Cane;David W. Christianson
中科院分区：
文献类型：
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作者：
L. Vedula;Yuxin Zhao;R. Coates;T. Koyama;D. Cane;David W. Christianson
Trichodiene合酶是一种萜类环化酶，其催化法呢基二磷酸（FPP）的环化以形成双环倍半萜烃类Trichodiene（89%）、至少五种倍半萜副产物（11%）和无机焦磷酸盐（PPi）。与2-氟法呢基二磷酸或4-甲基法呢基二磷酸的β-二烯合酶的孵育类似地产生倍半萜混合物，尽管通过底物衍生化引入了电子效应或空间体积。该酶的多功能性也在具有Mg 2 + 3-PPi和苄基三乙基铵阳离子的复合物的2.85 μ m分辨率的X射线晶体结构中得到证明，该复合物是催化中红没药基碳阳离子中间体的更大的模拟物。两者合计，这些发现表明，双烯合酶的活性位点是足够灵活的，以适应笨重和电子多样性的底物和中间体，这可能表明额外的潜力，这种萜类化合物环化酶的生物合成效用。
Trichodiene synthase is a terpenoid cyclase that catalyzes the cyclization of farnesyl diphosphate (FPP) to form the bicyclic sesquiterpene hydrocarbon trichodiene (89%), at least five sesquiterpene side products (11%), and inorganic pyrophosphate (PPi). Incubation of trichodiene synthase with 2-fluorofarnesyl diphosphate or 4-methylfarnesyl diphosphate similarly yields sesquiterpene mixtures despite the electronic effects or steric bulk introduced by substrate derivatization. The versatility of the enzyme is also demonstrated in the 2.85Å resolution X-ray crystal structure of the complex with Mg2+3-PPiand the benzyl triethylammonium cation, which is a bulkier mimic of the bisabolyl carbocation intermediate in catalysis. Taken together, these findings show that the active site of trichodiene synthase is sufficiently flexible to accommodate bulkier and electronically-diverse substrates and intermediates, which could indicate additional potential for the biosynthetic utility of this terpenoid cyclase.