Spontaneous and induced variability inStreptomyces nogalater producing nogalamycin

Abstract

Variability in the production of nogalamycin by Streptomyces nogalater var. nogalater was followed in untreated and mutagenized populations of the standard strain NRRL 3035 and its spontaneous variant K-18 using the method of agar blocks with subsequent tests under submerged conditions. In both strains the most active variants were obtained by natural selection without mutagenic treatment; in this way productivity increased by 108% after two selection steps. Treatment with UV-radiation did not yield variants with a highly increased activity. Gamma-radiation extended the variability but, at the same, substantially increased the number of non-producing and low-producing isolates. Relatively high yields of (+)-variants were obtained after treatment with nitrous acid but their activity did not reach that observed in the most active spontaneous variants.

Oxidative Cyclization in Natural Product Biosynthesis

“…nogalater (Scheme ). Unlike other anthracyclines, 250 is derived from a diglycosylated anthracycline scaffold 246 . The C 7 position is glycosylated with d -olivose, while the unusual bicyclic ring systems attached to C 1 and C 2 are derived from rhodosamine.…”

“…Following one hydrogen abstraction to yield the phenoxy radical 188, addition of the radical to the terminal double bond in the ester handle yields a new radical species 189 that is stabilized by the Allene oxides (193 and 196) are unstable vinyl epoxides and are key biosynthetic intermediates to a series of plant signaling molecules. 167 The epoxides are formed by the enzymatic dehydration and cyclization of lipoxygenase-catalyzed peroxidation of polyunsaturated fatty acids, such as linolenic acid (191) and arachidonic acid (194) (Scheme 32). The responsible enzyme for this transformation is the P450 allene oxide synthase (CYP74A).…”

“…532 PsoF was shown to be responsible for an additional epoxidation step to introduce an epoxide, which can be hydrolyzed to yield the trans diol found in 804. 530 Jasmonic acid (808), the important regulator in plant responses to biotic and abiotic stresses as well as in development, is a long-chain fatty acid-derived plant hormone biosynthesized from linolenic acid (191). 530 As shown in Scheme 112A, Shydroperoxide 192, installed by lipoxygenase, is the internal source of the resultant epoxide oxygen in the allene oxide 193 (see Scheme 32).…”

Biosynthesis of astromicin and related antibiotics. II. Biosynthetic studies with blocked mutants of Micromonospora olivasterospora.

“…Cosynthesis was performed according to the methods described by MCCORMICK et al11) and DELtc et al 11 Blocked mutants were incubated in SK, medium at 30°C for 3 days with shaking. One milliliter of the culture was transferred into 10 ml of fresh SKI medium and incubated at 30°C overnight.…”