Salamandamide Lipodipeptides Are Biosynthetic Intermediate Shunt Products of the Nonamodular Nonribosomal Peptide Assembly Lines of the Viscosin Family

Chemical investigation of a salamander-mucus-associated Pseudomonas tolaasii strain led to the isolation and chemical characterization of salamandamide A, a new lipo-dipeptide, along with known lipopeptides of the pseudodesmin and tolaasin class. Genome mining revealed that no specific gene cluster codes for the biosynthesis of salamandamide A. Stereochemical analyses and mutagenesis experiments linked the biosynthesis of the lipo-dipeptide salamandamide A to the NRPS gene cluster of the lipo-nonapeptide pseudodesmin. Further chemical investigations showed that this finding appears to be a broader concept and that all nonamodular NRPS gene clusters of the viscosin family were capable to produce, beside the expected lipo-nonapeptide, the corresponding lipo-dipeptide as a shunt product which also led to the discovery of salamandamide B from Pseudomonas lactis SS101.

对一株与蝾螈黏液相关的托拉斯假单胞菌（Pseudomonas tolaasii）菌株开展化学研究，成功分离得到新型脂二肽（lipo-dipeptide）蝾螈酰胺A（salamandamide A）并完成其化学表征，同时还获得了假德西明（pseudodesmin）与托拉斯素（tolaasin）类已知脂肽。基因组挖掘结果显示，未发现编码蝾螈酰胺A生物合成的专属基因簇。立体化学分析与诱变实验证实，该脂二肽蝾螈酰胺A的生物合成与脂九肽（lipo-nonapeptide）假德西明的非核糖体肽合成酶（Non-Ribosomal Peptide Synthetase，NRPS）基因簇相关联。进一步的化学研究表明，这一发现具备更广泛的普适性：黏菌素家族（viscosin family）的所有九模块非核糖体肽合成酶基因簇，除可合成预期的脂九肽外，还能够生成对应的脂二肽作为分流产物；该发现同时助力研究人员从乳酸假单胞菌（Pseudomonas lactis）SS101中分离得到蝾螈酰胺B（salamandamide B）。