Convergence of isoprene and polyketide biosynthetic machinery:: Isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis
Convergence of isoprene and polyketide biosynthetic machinery:: Isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis
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DOI：
10.1073/pnas.0603148103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Dorrestein, Pieter C.
中科院分区：
文献类型：
--
作者：
Calderone, Christopher T.;Kowtoniuk, Walter E.;Dorrestein, Pieter C.
来自枯草芽孢杆菌的pksX基因簇被预测编码一种尚未表征的杂交非核糖体颗粒/聚酮次生代谢物的生物合成。我们结合生化和质谱技术确定了AcpK、PksC、PksL、PksF、PksG、PksH和PksI蛋白的功能作用，我们得出结论，它们的作用是将醋酸盐衍生的p -甲基分支结合到乙酰乙酰基s载体蛋白上，并最终生成Delta(2)-异戊二烯- s载体蛋白。这项工作强调了质谱分析在阐明孤儿生物合成酶功能方面的力量，并详细介绍了单碳分支可以插入聚酮类结构的机制。该途径代表了构建戊烯基单元的非规范途径，并作为其他天然产物生物合成途径中类异戊二烯和聚酮生物合成歧管交叉的原型。
The pksX gene cluster from Bacillus subtilis is predicted to encode the biosynthesis of an as yet uncharacterized hybrid nonribosomal pepticle/polyketide secondary metabolite. We used a combination of biochemical and mass spectrometric techniques to assign functional roles to the proteins AcpK, PksC, PksL, PksF, PksG, PksH, and PksI, and we conclude that they act to incorporate an acetate-derived P-methyl branch on an acetoacetyl-S-carrier protein and ultimately generate a Delta(2)-isoprenyi-S-carrier protein. This work highlights the power of mass spectrometry to elucidate the functions of orphan biosynthetic enzymes, and it details a mechanism by which single-carbon ss-branches can be inserted into polyketide-like structures. This pathway represents a noncanonical route to the construction of prenyl units and serves as a prototype for the intersection of isoprenoid and polyketide biosynthetic manifolds in other natural product biosynthetic pathways.