在库拉菌素生物合成中，o-磺酸化作用先于聚酮脱羧链终止。
Polyketide decarboxylative chain termination preceded by o-sulfonation in curacin a biosynthesis.
机构信息
Life Sciences Institute, Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
出版信息
J Am Chem Soc. 2009 Nov 11;131(44):16033-5. doi: 10.1021/ja9071578.
Abstract
Biosynthetic innovation in natural product systems is driven by the recruitment of new genes and enzymes into these complex pathways. Here, an unprecedented decarboxylative chain termination mechanism is described for the polyketide synthase of curacin A, an anticancer lead compound isolated from the marine cyanobacterium Lyngbya majuscula. The unusual chain termination module containing adjacent sulfotransferase (ST) and thioesterase (TE) catalytic domains embedded in CurM was biochemically characterized. The TE was proved to catalyze a hydrolytic chain release of the polyketide chain elongation intermediate. Moreover, a selective ST-mediated sulfonation of the (R)-beta-hydroxyl group was found to precede TE-mediated hydrolysis, triggering a successive decarboxylative elimination and resulting in the formation of a rare terminal olefin in the final metabolite.
摘要
生物合成在天然产物系统中的创新是由新基因和酶的招募驱动的，这些新基因和酶被招募到这些复杂的途径中。在这里，描述了一种前所未有的聚酮合酶的脱羧链终止机制，这种聚酮合酶来自于抗癌先导化合物_curacin A，它是从海洋蓝藻 Lyngbya majuscula 中分离出来的。含有相邻的硫转移酶 (ST) 和硫酯酶 (TE) 催化结构域的不寻常的链终止模块在 CurM 中被生物化学表征。已经证明 TE 催化聚酮链延伸中间体的水解链释放。此外，发现 ST 介导的（R）-β-羟基的选择性磺化先于 TE 介导的水解，引发连续的脱羧消除，导致最终代谢物中形成罕见的末端烯烃。
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