Conditions for the production of jadomycin B byStreptomyces venezuelae ISP5230: Effects of heat shock, ethanol treatment and phage infection

Abstract

The novel benzoxazolophenanthridine antibiotic, jadomycin B, is produced by Streptomyces venezuelae ISP5230 following a 42 degrees C heat shock or exposure to ethanol. To further characterize these unusual culture conditions, studies were carried out using different media, varying nutrient content and concentrations, initial pH, and time of application of heat or ethanol stress. Highest titers of jadomycin B accumulated 48 h after S. venezuelae ISP5230 was inoculated into a D-galactose-L-isoleucine production medium (pH 7.5) which was supplemented with ethanol (6%, v/v) between 6 and 13 h. Cultures supplemented with ethanol later than 17 h post inoculation into the production medium produced little or no jadomycin B. Among other heat-shock inducing treatments examined, infection with phage SV1 was associated with increased jadomycin B production. Although jadomycin B titers showed little change with variations in the concentration of phosphate in the production medium, the nature of the nitrogen source was found to be important. Different colored pigments, presumed to be jadomycin B analogs, were formed when other amino acids replaced L-isoleucine in the medium as the sole nitrogen source. Increased jadomycin B titers accompanied increased L-isoleucine and D-galactose concentrations in the production medium.

Eight-Membered Ring-Containing Jadomycins: Implications for Non-enzymatic Natural Products Biosynthesis

“…HMBC correlations were observed from H3a to C3′ in all cases (Figure 3). If the configurations of 1a−1f contained five-membered oxazolone rings then the observed HMBC correlations between H3a and C3′ would represent unlikely 6 J couplings. In contrast, these correlations would represent much more likely 3 J couplings within eight-membered heterocycles.…”

Functional Analyses of Oxygenases in Jadomycin Biosynthesis and Identification of JadH as a Bifunctional Oxygenase/Dehydrase

“…CH56 -The in-frame deletion jadA mutant was cultured for jadomycin production by the procedure described by Doull et al (10) except that the culture medium was supplemented with 25 g/ml apramycin. Putative substrates (UWM6, 2,3-dehydro-UWM6, and rabelomycin) were added to the cultures at the time (6 h after inoculation) they were stressed with 6% (v/v) ethanol.…”

“…The phenanthridine ring system is plausibly derived by condensation of an amino acid with the postulated acid/ aldehyde intermediate (5), formed during angucyclic ring opening (7,9). Strengthening this possibility is the formation of jadomycin analogues when different amino acids are supplied as precursors (10,11). Until now, the only oxygenase gene identified in the jad biosynthetic cluster (Fig.…”

Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells

“…[1][2][3][4] Here we deal with jadomycin derivatives, which form a series of angucycline-derived molecules with a unique pentacyclic benz [b]oxazolophenanthridine skeleton, 5,6 produced by Streptomyces venezuelae ISP5230 under stress conditions, such as phage infection, heat and ethanol shock. 7 Jadomycin provides a model system to study secondary metabolism in streptomycetes, with unique biosynthetic and regulatory features.…”