Strepyrrolins A–E, five pyrrole–sesquiterpene hybrids from Streptomyces sp. KIB 015, revealing a new formation logic of pyrroles by isotope labeling

Abstract

Strepyrrolins A–E (1–5), five pyrrole–sesquiterpene hybrids sharing a 1,2,3-trisubstituted cyclopentanol terpene end-group, were isolated from an endophytic Streptomyces sp. KIB 015. Their structures were determined by single-crystal X-ray diffraction and spectroscopic methods. Feeding experiments with several isotope labeling substrates revealed that the terpene moiety in strepyrrolins is biosynthesized via the MEP (methylerythritol phosphate) pathway, and the pyrrole ring is constructed by a new formation logic in nature, using free ammonia and two C3 units like glycerol derivatives as potential substrates. An immunosuppressive screening assay showed that 3 could inhibit T cell proliferation with IC₅₀ values of 1.2 μM (with anti-CD3/anti-CD28 mAbs stimulation) and 1.5 μM (with phytohemagglutin stimulation), in the way of inducing T cell cycle arrest in the G₀/G₁ phase.