Acyl-carrier protein-phosphopantetheinyltransferase partnerships in fungal fatty acid synthases.
Acyl-carrier protein-phosphopantetheinyltransferase partnerships in fungal fatty acid synthases.
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DOI：
10.1002/cbic.200700659
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发表时间：
2008-07-02
期刊：
影响因子：
3.2
通讯作者：
Townsend, Craig A.
中科院分区：
文献类型：
--
作者：
Crawford, Jason M.;Vagstad, Anna L.;Ehrlich, Kenneth C.;Udwary, Daniel W.;Townsend, Craig A.
脂肪酸的合成是能量储存和细胞结构完整性的基本代谢过程。饱和脂肪酸的组装是通过脂肪酸合成酶(FASS)实现的，FASS通过重复的脱羧基克莱森缩合反应以及随后的还原和脱水步骤将乙酰基和丙二酸基-COA结合在一起。[1]在哺乳动物中，7个催化域由一个基因编码，产生α2-同源二聚体蛋白。一种酰基载体蛋白(ACP)被CoA衍生的手臂翻译后修饰，通过磷酸铁蛋白转移酶(PPT)在迭代催化循环中通过硫酯键连接生长中的脂肪酸。这种对全息ACP臂的附着在合成过程中培养了高有效底物浓度。然而，在真菌中，八个催化域被分成两个亚基，一个结构上不同的α6β6规范复合体以辅酶A酯的形式释放最终产物，而不是像动物FAS那样以游离酸的形式释放最终产物。几个已知的例子在真菌中已知，在真菌中，专门的FAS已经进化成在次生代谢途径中与聚酮合成酶(PKS)相互作用。[2]例如，去甲酸合成酶(NORS)由一对脂肪酸亚基，HexA和HexB，[3]组成，它合成一个C6-脂肪酸起始单元，以启动相关的PKS，Pks A，形成黄曲霉毒素(1)前体(方案1)根据大小排除层析估计，这些亚基结合成大约1.4mda物种，它们被认为形成与初级真菌代谢的Fas截然不同的α2β2γ2复合体。[4]己酰辅酶A在体外试验中没有被检测到作为游离中间体，这表明，但没有证明，Fas和PKS亚基之间可以发生直接转移。在伴随的PKS中发现了一个起始单元：ACP转酰基酶(SAT)结构域，它具有C6链长特异性，并催化转移到PksA ACP上，连接脂肪酸和聚酮的合成。[5]初级和次级代谢Fas在蛋白质组织上的巨大差异反映了不同的进化史。
The synthesis of fatty acids is an essential primary metabolic process for energy storage and cellular structural integrity. Assembly of saturated fatty acids is achieved by fatty acid synthases (FASs) that combine acetyl-and malonyl-CoAs by repetitive decarboxylative Claisen condensations with subsequent reduction and dehydration steps.[1] In mammals seven catalytic domains are encoded by a single gene, giving rise to an α2-homodimeric protein. An acyl-carrier protein (ACP) that is post-translationally modified with a CoA derived arm by a phosphopantetheinyltransferase (PPT), tethers the growing fatty acid via a thioester linkage during the iterative catalytic cycle. Such attachment to the holo-ACP arm fosters high effective substrate concentrations during the synthesis. In fungi, however, eight catalytic domains are divided between two subunits, and an architecturally distinct α6β6 canonical complex releases the final product as a CoA ester rather than as a free-acid, as occurs with animal FASs.Several examples are known in fungi where dedicated FASs have evolved to interact with polyketide synthases (PKSs) in secondary metabolic pathways.[2] For example, norsolorinic acid synthase (NorS) is comprised of a pair of fatty acid subunits, HexA and HexB,[3] that synthesize a C6-fatty acid starter unit to prime the associated PKS, PksA, in the formation of the aflatoxin (1) precursor, norsolorinic acid (2).(Scheme 1) These subunits associate into an approximately 1.4 MDa species as estimated by size exclusion chromatography, and they are thought to form an α2β2γ2 complex that is quite distinct from the FAS of primary fungal metabolism.[4] Hexanoyl-CoA was not detected as a free intermediate in in vitro assays, suggesting, but not proving, that a direct transfer could take place between the FAS and PKS subunits. A starter unit: ACP transacylase (SAT) domain in the accompanying PKS was identified that exhibited C6-chain length specificity and catalyzed transfer to the PksA ACP to bridge fatty acid and polyketide synthesis.[5] Such drastic differences in the protein organization of primary and secondary metabolic FASs reflect different evolutionary histories.
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影响因子：
--
作者：
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通讯作者：
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影响因子：
56.9
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