Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides
Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides
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DOI：
10.1038/s41557-020-0508-2
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发表时间：
2020-07-27
期刊：
影响因子：
21.8
通讯作者：
Onaka, Hiroyasu
中科院分区：
文献类型：
--
作者：
Kozakai, Ryosuke;Ono, Takuto;Onaka, Hiroyasu
goadvionins（混合脂肽抗生素）的生物合成尚不完全清楚。现已鉴定出一种不寻常的酰基转移酶 GdvG，并显示其可催化酰基载体蛋白束缚的超长链脂肪酸与八残基核糖体合成和翻译后修饰的肽之间的缩合反应。通过串联质谱法确定了超长酰基链中官能团的位置。脂肪酸和肽的融合扩大了天然产物的结构多样性；然而，聚酮化合物/核糖体合成的和翻译后修饰的肽（PK/RiPPs）杂合脂肽相对罕见。在这里，我们报告了一个名为 goadvionins 的 PK/RiPP 家族，它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 包含三甲基铵 32 个碳酰基链和具有 avionin 结构的八个残基 RiPP。通过自由基诱导解离串联质谱法测定了极长酰基链中六个羟基和一个双键的位置，该质谱法与自由基离子种类碰撞产生 C-C 键断裂片段。 GdvG 属于 Gcn5 相关的 N-乙酰转移酶超家族。与传统的酰基转移酶不同，GdvG 将与酰基载体蛋白相连的很长的酰基链转移到 RiPP 部分的 N 端氨基。 侧翼为 PK/脂肪酸和 RiPP 生物合成基因的 gdvG 同源物广泛分布于微生物物种中，这表明酰基转移酶催化的 PK 和 RiPP 缩合是一种 类似脂肽生物合成的一般策略。
The biosynthesis of goadvionins-hybrid lipopeptide antibiotics-is not fully understood. An unusual acyltransferase, GdvG, has now been identified and shown to catalyse a condensation reaction between an acyl-carrier-protein-tethered very-long-chain fatty acid and an eight-residue ribosomally synthesized and post-translationally modified peptide. The position of functional groups in the very-long acyl chain have been determined by tandem mass spectrometry.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-relatedN-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.gdvGhomologues 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.