Structural Determination of Hypnosin, a Spore Germination Inhibitor of Phytopathogenic Streptomyces sp. Causing Root Tumor in Melon (Cucumis sp.)

Abstract

The structure of a germination inhibitor, hypnosin, isolated from phytopathogenic Streptomyces sp. causing root tumor of melon was determined to be 3-acetylaminopyrazine-2-carboxylic acid (1) by mass spectrometry, computational chemical prediction of UV spectrum, and synthesis of candidates. The structure-activity relationship of hypnosin and anthranilic acid was examined, and it was concluded that pyrazinecarboxylic acid or pyridine-2-carboxylic acid was the fundamental structure with activity, that methylation of the carboxyl group or decarboxylation destroyed activity, and that the presence of an amino group was inhibitory to the activity, whereas acetylation or deletion of an amino group enhanced activity. Hypnosin inhibited spore germination of some Streptomyces spp. in addition to the species with which it was isolated.

Physiological role of germicidins in spore germination and hyphal elongation in Streptomyces coelicolor A3(2)

“…CB-1-1, from which hypnosin was originally isolated (IC 50 ¼0.25 mg ml À1 ). 8,9 Quantitative estimation of germicidins and hypnosin in S. coelicolor spores From 50 cultured petri dishes (9 cm i.d.) of S. coelicolor A3(2), B1.0Â10 10 spores were collected by the glass-bead-based method and 11.9 mg of ethyl acetate-soluble extract was obtained.…”

“…We then searched for an inhibitor in agar cultures, isolated 0.25 mg of an inhibitor from 3500 cultured petri dishes, and named this inhibitor hypnosin (5). 8,9 Hypnosin selectively inhibits spore germination and its inhibitory activity is removable by washing hypnosin-treated spores in water. Hypnosin showed activity at a concentration equivalent to that in the culture supernatant during germination; thus, we identified it as the self-inhibitor of the phytopathogenic Streptomyces sp.…”

Studies on bioactive natural products involved in the growth and morphological differentiation of microorganisms

“…8) was determined by mass spectrometry, computational chemical prediction of the UV spectrum, and synthesis of candidates. 30) This was the first finding of the compound as a natural product, and we named it hypnosin after the god of sleep.…”