Nonribosomal peptide synthetases (NRPSs) increase the chemical diversity of their products by acquiring tailoring domains. Linear gramicidin synthetase starts with a tailoring formylation (F) domain, which likely originated from a sugar formyltransferase (FT) gene. Here, we present studies on an Anoxybacillus kamchatkensis sugar FT representative of the prehorizontal gene transfer FT. Gene cluster analysis reveals that this FT acts on a UDP-sugar in a novel pathway for synthesis of a 7-formamido derivative of CMP-pseudaminic acid. We recapitulate the pathway up to and including the formylation step in vitro, experimentally demonstrating the role of the FT. We also present X-ray crystal structures of the FT alone and with ligands, which unveil contrasts with other structurally characterized sugar FTs and show close structural similarity with the F domain. The structures reveal insights into the adaptations that were needed to co-opt and evolve a sugar FT into a functional and useful NRPS domain.

中文翻译：

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新型甲酰基转移酶的结构洞察力和向非核糖体肽合成酶定制域的演变。

非核糖体肽合成酶（NRPS）通过获取定制域来增加其产品的化学多样性。线性短杆菌肽合成酶以定制的甲酰化（F）域开始，该域可能起源于糖甲酰基转移酶（FT）基因。在这里，我们目前对代表水平前基因转移FT的堪培克无氧杆菌糖FT的研究。基因簇分析表明，该FT以新颖的途径作用于UDP糖，用于合成CMP伪氨基酸的7-甲酰胺基衍生物。我们概述了体外的甲酰化步骤，包括甲酰化步骤，通过实验证明了金融时报的作用。我们还介绍了FT单独和配体的X射线晶体结构，揭示了与其他结构特征糖FT的对比，并显示了与F结构域的紧密结构相似性。这些结构揭示了对将FT糖选择并进化为功能性和有用的NRPS结构域所需的适应性见解。