A New Teleocidin Analog from Streptomyces sp. MM216-87F4 Induces Substance P Release from Rat Dorsal Root Ganglion Neurons

Abstract

A new teleocidin analog was isolated from the fermentation medium of Streptomyces sp. MM216-87F4 and its structure was elucidated as 14-O-(Nacetylglucosaminyl) teleocidin A (GlcNAc-TA). GlcNAc-TA induces the translocation of protein kinases Ca and q fused with enhanced green fluorescent protein (PKCa -EGFP and PKCq -EGFP) to the plasma membrane in stable transfectants, and reduces intracellular calcium mobilization induced by agonists of G-protein coupled receptors in various cell lines without causing irritation of the mouse ear. Further, GlcNAc-TA sensitizes the release of excitatory neuropeptides substance P induced by capsaicin from primary-cultured dorsal root ganglion (DRG) neurons of the rat and GlcNAc-TA alone also triggers substance P release in a dose-dependent manner. This study provides the first observation that a teleocidin analog without a free hydroxyl group at C-14 acts as a PKC activator and directly induces the release of excitatory neuropeptide.

A comprehensive review of glycosylated bacterial natural products

“…Miscellaneous peptides that lack anti-infective related activity are summarized herein. These include aeruginosides, 1113 aeruginosins, 1114 muraceins, 1115 enkastines, 1116 banyasides, 1117 phosphoramidon, 1118 GlcNAc-TA, 1119 mycothiols, 47,1120 bacillithiols, 1121 and alanopine 1122 from Streptomyces , Nostoc , Nocardia , Planktothrix , Bacillus , Staphylococcus Providencia , Proteus and Oscillatoria (Fig. 51).…”

“…1118 GlcNAc-TA is a prenylated indolactam C-14- O -glycoside ( N -acetyl-β- d -glucosamine, 153 ). 1119 This is the only naturally-occurring teleocidin glycoside and is a small molecule activator of protein kinase C and induces the release of excitatory neuropeptides.…”

Marine Indole Alkaloids

“…The teleocidin analog 14- O -( N -acetylglucosaminyl) teleocidin A (GlcNAc-TA) ( 447 ) was isolated from Streptomyces sp. MM216-87F4 and was shown to affect the release of the neurotransmitter substance P from Dorsal Root Ganglia (DRG) neurons via protein kinase C (PKC) pathway ( Figure 72 ) [ 191 ]. JBIR-31 ( 448 ) was isolated from Streptomyces sp.…”

JBIR-31, a new teleocidin analog, produced by salt-requiring Streptomyces sp. NBRC 105896 isolated from a marine sponge

“…32 Recently, it has been reported that a teleocidin derivative, 14-O-(N-acetylglucosaminyl) teleocidin A, induces the translocation of protein kinases Ca and y, and sensitizes the release of excitatory neuropeptide substance P induced by capsaicin from primary-cultured dorsal root ganglion neurons of the rat. 33 Because teleocidin analogs possess various biological activities, studies on detailed biological activities against MPM cells by 1 and teleocidin A 1 are now underway.…”