Discovery, production and purification of the Na+, K+ activated ATPase inhibitor, L-681,110 from the fermentation broth of Streptomyces sp. MA-5038.
The maximum yield for the production of L-681,110 by Streptomyces sp. MA-5038 (ATCC 31587) was observed after 5 days' incubation at 28 degrees C and pH about 8.3. L-681,110 was isolated from the fermentation broth by acetone extraction of the mycelia, absorption to Amberlite XAD-2 resin and two separations by thin-layer chromatography. The structure of L-681,110 was found to consist of a sixteen-membered lactone with a new type of substitution. The inhibition of ATPase, activity against Caenorhabditis elegans and stimulation of gamma-aminobutyric acid release indicate that L-681,110 possesses some characteristics of both oligomycin and avermectin. L-681,110 was also active against tapeworm and ticks in an in vivo assay.
D000818:Animals; D001921:Brain / Q000187:drug effects; D002107:Caenorhabditis / Q000187:drug effects; D002589:Cestoda / Q000187:drug effects; D005285:Fermentation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007783:Lactones / Q000302:isolation & purification* / Q000494:pharmacology; D008297:Male; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000378:metabolism*; D013987:Ticks / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007783:Lactones; D005680:gamma-Aminobutyric Acid; C043472:L 681110; D000254:Sodium-Potassium-Exchanging ATPase