LC-MS-Guided Isolation of Cyanogripeptides A-C, Cyclolipopeptides with β-Methyl-Leucine Residues, from an Actinoalloteichus cyanogriseus LHW52806.

Cyanogripeptides A-C ( 1 - 3 ), three new cyclolipopeptides with unusual β-methyl-leucine residues, were identified from an Actinoalloteichus cyanogriseus LHW52806 using an LC-MS-guided strategy. The structures of compounds 1 - 3 were elucidated by 1D/2D NMR, HR-MS/MS, and the advanced Marfey's method. The absolute configuration of the β-methyl-leucine residue was determined by a combination of stereoselective biosynthesis of (2 S ,3 R )-β-methyl-leucine, racemization to its epimer (2 R ,3 R )-β-methyl-leucine, and the advanced Marfey's method. The biosynthetic pathway of cyanogripeptides was deduced by analyzing the genome of A . cyanogriseus LHW52806. Compound 3 exhibited antibacterial activity against Helicobacter pylori G27, Helicobacter pylori 26695, and Mycolicibacterium smegmatis ATCC607 with MIC values of 32 μg/mL.