Sadopeptins A and B, Sulfoxide- and Piperidone-Containing Cyclic Heptapeptides with Proteasome Inhibitory Activity from a sp.

New sulfur-bearing natural products, sadopeptins A and B ( and ), were discovered from sp. YNK18 based on a targeted search using the characteristic isotopic signature of sulfur in mass spectrometry analysis. Compounds and were determined to be new cyclic heptapeptides, bearing methionine sulfoxide [Met(O)] and 3-amino-6-hydroxy-2-piperidone (Ahp), based on 1D and 2D NMR spectroscopy along with IR, UV, and MS. The configurations of sadopeptins A and B ( and ) were established via the analysis of the ROESY NMR correlation, oxidation, Marfey's method, and circular dichroism (CD) spectroscopy. The bioinformatics analysis of the full sp. YNK18 genome identified a nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster (BGC), and a putative biosynthetic pathway is proposed. Sadopeptins A and B displayed proteasome-inhibitory activity without affecting cellular autophagic flux.