Iminimycin A, the new iminium metabolite produced by Streptomyces griseus OS-3601

Abstract

A new natural product, designated iminimycin A, was isolated from the cultured broth of a streptomycin-producing microbial strain, Streptomyces griseus OS-3601, via a physicochemical screening method using HP-20, silica gel and ODS column chromatographies and subsequent preparative HPLC. Iminimycin A is an indolizidine alkaloid, containing of an unusual iminium group and a cyclopropane ring with a triene side chain. The absolute configuration of iminimycin A was elucidated by NMR studies and electronic circular dichroism analysis. Iminimycin A shows anti-bacterial activity against Bacillus subtilis, Kocuria rhizophila and Xanthomonas campestris pv. orizae, and cytotoxic activity against HeLa S3 and Jurkat cells with IC50 values of 43 and 36 μM, respectively.

The “Three Cs” of Novel Antibiotic Discovery and Production through Synthetic Biology: Biosynthetic Gene Clusters, Heterologous Chassis, and Synthetic Microbial Consortia

“…Conversely, there are also many antibiotics which have been elucidated from crude cell culture extracts but have not been linked with the corresponding gene cluster—iminimycin A and 1‐methoxypyrrole‐2‐carboxamide (from S. griseus and Streptomyces griseocarneus , respectively) are examples of this. “Orphan products” (not linked to a gene cluster) may be interesting to investigate in the future for improvement of yield or strength, especially with the advent of Pep2Path for the mass‐spectrometry‐based mining of novel peptide metabolites . A high‐throughput screening platform termed “SLAY” (Surface Localized Antimicrobial Display) has also recently been published for the testing of novel peptide antimicrobials .…”

Mumiamicin: Structure and bioactivity of a new furan fatty acid from <i>Mumia</i> sp. YSP-2-79

“…oryzae KB 88, were incubated at 37∞C for 24 h. Fungi and X. campestris pv. oryzae KB 88 were incubated at 27∞C for 48 h. The cytotoxic activity of 1 against HeLa S3 and Jurkat cells were evaluated, according to previously reported techniques (Nakashima et al, 2016a). Scavenging effects on hydroxyl radical (·OH) and singlet oxygen ( 1 O 2 ): Both ·OH and 1 O 2 scavenging assays were essentially identical to those previously described (Katsuda et al, 2015).…”

Absolute configuration of iminimycin B, a new indolizidine alkaloid, from Streptomyces griseus OS-3601

“…8 Iminimycin A is an indolizidine alkaloid, consisting of an octahydroindolizine skeleton with a triene side chain and a cyclopropane ring, and the most distinctive feature of this compound is to have an unusual iminium group. 5 In PC screening for discovery of new compounds from the culture broth of this strain, an unidentified compound with an absorption maximum at 279 and 394 nm and molecular ion peak at m/z 399 was observed in the other ODS fraction without iminimycin A. This compound, designated iminimycin B (1) , w a s a n e w indolizine alkaloid possessing a N-acetyl-cysteine and a pyridinium ( Figure 1) instead of iminium moiety of iminimycin A.…”

“…The strain OS-3601 was isolated as a streptomycinproducing strain at Aso, Kumamoto-Prefecture, Japan in 1972, and preserved for over 40 years. 5 Many indolizine alkaloids with their unique structures and biological activities were mainly isolated from metabolites plants, frogs and ants. 6 The alkaloid compounds have been also found to produced by some actinomycete strains, but a few only compounds are extant.…”