Graduate School of Agricultural and Life Sciences, Department of Biotechnology, The University of Tokyo, Tokyo, Japan.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Nat Chem. 2020 Sep;12(9):869-877. doi: 10.1038/s41557-020-0508-2. Epub 2020 Jul 27.
Fusions of fatty acids and peptides expand the structural diversity of natural products; however, polyketide/ribosomally synthesized and post-translationally modified peptides (PK/RiPPs) hybrid lipopeptides are relatively rare. Here we report a family of PK/RiPPs called goadvionins, which inhibit the growth of Gram-positive bacteria, and an acyltransferase, GdvG, which catalyses the condensation of the PK and RiPP moieties. Goadvionin comprises a trimethylammonio 32-carbon acyl chain and an eight-residue RiPP with an avionin structure. The positions of six hydroxyl groups and one double bond in the very-long acyl chain were determined by radical-induced dissociation tandem mass spectrometry, which collides radical ion species to generate C-C bond cleavage fragments. GdvG belongs to the Gcn5-related N-acetyltransferase superfamily. Unlike conventional acyltransferases, GdvG transfers a very long acyl chain that is tethered to an acyl carrier protein to the N-terminal amino group of the RiPP moiety. gdvG homologues flanked by PK/fatty acid and RiPP biosynthesis genes are widely distributed in microbial species, suggesting that acyltransferase-catalysed condensation of PKs and RiPPs is a general strategy in biosynthesis of similar lipopeptides.
脂肪酸和肽的融合扩展了天然产物的结构多样性；然而，聚酮/核糖体合成和翻译后修饰肽（PK/RiPPs）杂合脂肽相对较少。在这里，我们报告了一类称为 goadvionin 的 PK/RiPPs，它们抑制革兰氏阳性菌的生长，以及一种酰基转移酶 GdvG，它催化 PK 和 RiPP 部分的缩合。Goadvionin 由一个三甲基铵 32 碳酰基链和一个具有 avionin 结构的八残基 RiPP 组成。非常长的酰基链中六个羟基和一个双键的位置通过自由基诱导的解离串联质谱法确定，该方法碰撞自由基离子物种以生成 C-C 键断裂片段。GdvG 属于 Gcn5 相关 N-乙酰基转移酶超家族。与传统的酰基转移酶不同，GdvG 将连接在酰基辅酶 A 上的非常长的酰基链转移到 RiPP 部分的 N 端氨基上。由 PK/脂肪酸和 RiPP 生物合成基因侧翼的 gdvG 同源物广泛分布于微生物物种中，表明 PK 和 RiPP 的酰基转移酶催化缩合是类似脂肽生物合成的一般策略。
