WS9326H, an Antiangiogenic Pyrazolone-Bearing Peptide from an Intertidal Mudflat Actinomycete

Abstract

WS9326H (1), a new cyclic peptide, was isolated from a mudflat-derived Streptomyces strain. Based on analysis by 1D/2D NMR, UV spectroscopy, and mass spectrometry, compound 1 was determined to have the gross structure of a cyclic heptapeptide bearing an unprecedented pyrazolone ring connected to a d-arabinitol via an amide bond. The absolute configuration of 1 was established by multistep chemical derivatizations, comprehensive NMR, and LC/MS analyses of the derivatives and quantum mechanics-based computational methods. WS9326H (1) displayed significant antiangiogenesis activity.

An Unusual Type II Polyketide Synthase System Involved in Cinnamoyl Lipid Biosynthesis

“…(Figures 1 A, S1). Notably, CL containing compounds display a broad range of physiological activities, including but not limited to antiangiogenic, [7] antitumor, [5] antibacterial, [1] antifungal, [8] antituberculosis, [9, 10] and enzyme inhibitor [11, 12] . For example, atratumycin displays potent antituberculosis activity, [10] skyllamycin A is a potent inhibitor of the platelet‐derived growth factor (PDGF) signaling pathway, [6] and serpentemycin A possesses a strong inhibitory activity against glycosyltransferase [11]…”

“…This method is able to tell us the intracellular assembly details happening on CPs, and would significantly contribute to disclosing the mysteries of CP-dependent biosynthetic machineries. Furthermore, given the conservative skeleton, flexible post modifications, [5,7,9,28] and more importantly discrete PKS proteins, CL containing compounds hold great potentials in combinatorial biosynthesis.…”

“…Up to now, only a handful of CL containing compounds have been reported, such as youssoufenes (1-5), [1] serpentene (6), [2] diacidene, [3] lahorenoic acids, [4] and cinnamoyl-containing nonribosomal peptides (CCNPs) (kitacinnamycins, [5] skyllamycins, [6] et al) (Figures 1 A, S1). Notably, CL containing compounds display a broad range of physiological activities, including but not limited to antiangiogenic, [7] antitumor, [5] antibacterial, [1] antifungal, [8] antituberculosis, [9,10] and enzyme inhibitor. [11,12] For example, atratumycin displays potent antituberculosis activity, [10] skyllamycin A is a potent inhibitor of the plateletderived growth factor (PDGF) signaling pathway, [6] and serpentemycin A possesses a strong inhibitory activity against glycosyltransferase.…”

Unprecedented Noncanonical Features of the Nonlinear Nonribosomal Peptide Synthetase Assembly Line for WS9326A Biosynthesis

“…sp. SNM55, [9, 10] S. calvus ATCC 13382, [11] and S. asterosporus DSM 41452 [12] ) have also been identified to produce 1 and its congeners. WS9326A has remarkable structural features, including the ( E )‐2,3‐didehydrotyrosine (ΔTyr) residue, which has not been found in other NRPs.…”

Depsidomycins B and C: New Cyclic Peptides from a Ginseng Farm Soil-Derived Actinomycete

“…Our time-course chemical analysis of bacterial metabolites using LC/MS chemical profiling yielded new chemotypes, demonstrating the value of chemical analysis-based research in natural products chemistry. A recent example of the success of such a method is the discovery of a novel pyrazolone-bearing metabolite from a Streptomyces strain collected in an intertidal mudflat [ 3 ]. A Deinococcus strain isolated from the gut of the carpenter ant, Camponotus japonicus , was found to produce new aminoglycolipids [ 4 ].…”