Pepticinnamins N, O and P, cytotoxic non-ribosomal peptides from a Soil-Derived Streptomyces mirabilis P8-A2

Cinnamoyl moiety containing non-ribosomal peptides represented by pepticinnamin E, are a growing family of natural products isolated from different Streptomyces and possess diverse bioactivities. A soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E (1) and its analogues, pepticinnamins N, O and P (2-4), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey´s reactions. These new compounds exerted modest growth inhibitory effect against the LNCaP and C4-2B prostate cancer lines, respectively, with pepticinnamin O being the most active.