The carbon chain-selective adenylation enzyme TamA: the missing link between fatty acid and pyrrole natural product biosynthesis.
The carbon chain-selective adenylation enzyme TamA: the missing link between fatty acid and pyrrole natural product biosynthesis.
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DOI：
10.1039/c8ob00441b
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发表时间：
2018-04-18
影响因子：
3.2
通讯作者：
Campopiano DJ
中科院分区：
文献类型：
--
作者：
Marchetti PM;Kelly V;Simpson JP;Ward M;Campopiano DJ
TAMA是一种腺化酶，它选择和激活脂肪酸，以合成Tambjamine。海洋细菌衣状假交替单胞菌产生联吡咯抗生素TAMBJAME YP1。这种天然产物由常见的氨基酸和脂肪酸组成，其生物合成途径由操纵子编码，该操纵子包含19个基因。这些蛋白中的每一个在Tambjamine生物合成中扮演的确切角色尚不清楚。在这里，我们提供了TAMA启动合成并控制必需的TAMBJAME脂肪胺尾巴的链长的证据。序列分析表明，不寻常的TAMA是由一个N-端腺苷化(ANL)结构域与一个C-端酰基载体蛋白(ACP)融合而成的。重组TAMA的质谱分析显示，C11和C12酰基腺苷中间体令人惊讶地存在。当磷酸丙氨酸(4‘-PP)臂连接到ACP上时，观察到ACP结构域的酰化。我们还表明，TAMA可以将C6-C13链长的脂肪酸转移到分离的ACP结构域。因此，TAMA通过连接脂肪酸和吡咯的生物合成途径，弥合了初级和次级新陈代谢之间的差距。
TamA is the adenylating enzyme that selects and activates fatty acids for tambjamine biosynthesis. The marine bacterium Pseudoalteromonas tunicata produces the bipyrrole antibiotic tambjamine YP1. This natural product is built from common amino acid and fatty acid building blocks in a biosynthetic pathway that is encoded in the tam operon which contains 19 genes. The exact role that each of these Tam proteins plays in tambjamine biosynthesis is not known. Here, we provide evidence that TamA initiates the synthesis and controls the chain length of the essential tambjamine fatty amine tail. Sequence analysis suggests the unusual TamA is comprised of an N-terminal adenylation (ANL) domain fused to a C-terminal acyl carrier protein (ACP). Mass spectrometry analysis of recombinant TamA revealed the surprising presence of bound C11 and C12 acyl-adenylate intermediates. Acylation of the ACP domain was observed upon attachment of the phosphopantetheine (4′-PP) arm to the ACP. We also show that TamA can transfer fatty acids ranging in chain length from C6–C13 to an isolated ACP domain. Thus TamA bridges the gap between primary and secondary metabolism by linking fatty acid and pyrrole biosynthetic pathways.
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影响因子：
14.8
作者：
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通讯作者：
Sternberg MJ
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