Biotransformation of selamectin with Streptomyces lydicus SX-1298 using a novel static agar fermentation system with Reemay mesh.

A novel approach to biotransformation is described using a solid medium matrix and Reemay mesh that gives efficient biotransformation of compounds with minimal matrices in the ensuing gum solids. Using this approach with a newly isolated biotransforming organism, Streptomyces lydicus SX1298, a series of hydroxylations and an O-demethylation is described for selamectin the first endectocide for cats and dogs.

Avermectins and flea control: structure-activity relationships and the selection of selamectin for development as an endectocide for companion animals.

Evaluation of a wide range of avermectin derivatives for flea activity in an in vitro feeding screen using the cat flea, Ctenocephalides felis, revealed a narrow structure-activity relationship (SAR) with activity surprisingly associated with monosaccharides and especially their C-5-oximes. We discovered commercially exploitable flea activity in a single compound, selamectin 33, which also possessed the necessary antiparasitic spectrum and margin of safety for development as a broad-spectrum companion animal endectocide.

Selamectin: a novel broad-spectrum endectocide for dogs and cats.

Selamectin, 25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22, 23-dihydro-5-(hydroxyimino)-avermectin B1 monosaccharide, is a novel endectocide with a unique combination of efficacy and safety in dogs and cats following both oral and topical administration. The compound is active against fleas and ticks, intestinal hookworms and ascarids, and immature heartworms. Also it is well tolerated at higher dosages than 22,23-dihydroavermectin B1a (DHAVM) or milbemycin oxime in Collies, which is a breed known to exhibit idiosyncratic sensitivity to avermectins.

Novel erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL 2338 pIG1. I. Fermentation, isolation and biological activity.

In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora erythraea, was integrated into the S. erythraea chromosome, effectively replacing the natural erythromycin loading domain with the avermectin loading domain. In this paper, we report the feeding of short-chained fatty acids to this recombinant strain, and its parent, NRRL 2338. Both strains incorporated exogenously supplied fatty acids to produce novel, biologically active, C-13 substituted erythromycins.

C-13 beta-acyloxymilbemycins, a new family of macrolides. Discovery, structural determination and biological properties.

A family of novel milbemycins possessing C-13 beta-acyloxy substitution was produced by Streptomyces hygroscopicus ATCC 53718. These compounds were detected by HPLC diode array analysis and possess anthelmintic and ectoparasiticidal activity. The origin of the oxygen atom at C-13 is discussed.

Novel avermectins produced by mutational biosynthesis.

Avermectins with a wide range of novel C-25 substituents have been prepared by feeding carboxylic acids or their biosynthetic precursors to a Streptomyces avermitilis mutant strain ATCC 53568. This organism lacks the ability to form isobutyric and S-2-methylbutyric acids from their 2-oxo acid precursors and thus is unable to produce natural avermectins unless supplied with these acids. The novel avermectins produced by mutational biosynthesis possess broad-spectrum antiparasitic activity.

UK-69,753, a novel member of the efrotomycin family of antibiotics. I. Taxonomy of the producing organism, fermentation and isolation.

UK-69,753 is a novel antibiotic structurally related to efrotomycin and factumycin, produced by a new strain of Amycolatopsis orientalis (ATCC 53550). The antibiotic potency in the fermentation broth was monitored by HPLC with diode array detection. A six tube counter current distribution was used to purify UK-69,753.

UK-63,052 complex, new quinomycin antibiotics from Streptomyces braegensis subsp. japonicus; taxonomy, fermentation, isolation, characterisation and antimicrobial activity.

UK-63,052 complex, a new group of quinomycin-like antibiotics comprising UK-63,052 (factor A), UK-63,598 (factor C), UK-65,662 (factor B) and several uncharacterised minor components, is produced by a new subspecies of the genus Streptomyces for which the name Streptomyces braegensis Dietz subsp. japonicus, is proposed. The strain, N617-29, is characterised by a negative melanin reaction, grey aerial mycelium, spiral spore chains and smooth or slightly warty spores. Structure determination has identified UK-63,052, C56H68N10O14S2, UK-63,598, C53H62N10O14S2 and UK-65,662, C55H66N10O14S2 as quinaldic acid substituted quinomycins with unusual bridgehead sulfur substitution as shown in Fig. 3.