Glucose Repression of Carbon Source Uptake and Metabolism in Streptomyces coelicolor A3(2) and its Perturbation in Mutants Resistant to 2-Deoxyglucose

Abstract

A newly devised method to obtain diffuse growth of Streptomyces coelicolor A3(2) in liquid minimal medium was used to study glucose repression. Although diauxic growth was not obtained, glucose repression of uptake of 14C-labelled carbon sources was demonstrated. Active, arabinose-induced, arabinose transport was repressed at the level of transcription by glucose. Of two glycerol-inducible glycerol transport systems, one was glucose-inhibited but not repressed (and operated by facilitated diffusion), whilst the other (an active transport system) was glucose-repressed. Active transport systems for galactose and fructose which did not require induction by their respective sugars were both inhibited by glucose. Galactose-and fructosemetabolizing enzymes were inducible by the respective sugars, but only in the absence of glucose. This was because glucose both inhibited galactose and fructose transport and repressed the metabolic enzymes concerned. Constitutive active glucose uptake was also demonstrated in arabinose-grown cells. Mutants that grew on arabinose or glycerol in the presence of 2-deoxyglucose were glucose-derepressed for both soluble carbon source utilization and extracellular agarose.*Three glucose-derepressed mutants were studied in detail. One of these could not utilize glucose (and probably lacks glucose kinase), whilst the other two could utilize glucose to differing degrees.

Substrate induction and glucose repression of maltose utilization by Streptomyces coelicolor A3(2) is controlled by malR, a member of the lacI–galR family of regulatory genes

“…Thus, MalR is required for both substrate induction and glucose repression of malE expression. While S. coelicolor grows poorly on maltose as sole carbon source (Hodgson, 1982; G. P. van Wezel, J. White, M. J. Bibb and P. O. Postma, submitted), the malR mutants grew much better than the parental strain, perhaps because of elevated levels of maltose uptake.…”

Carbon source regulation of antibiotic production

“…High concentrations of sugar elicit CCR over the use of alternative carbon sources and the synthesis of several secondary metabolites. Glucose repression in S. coelicolor operates at the transcriptional level to repress enzymes involved in the use of glycerol, arabinose, fructose and galactose 122 and this effect seems to be due to either intermediates of carbohydrate catabolism, for example, fructose 1,6-diphosphate and glucose 6-phosphate 123,124 or enzymes of the glucose catabolic pathway, such as glucose kinase. [125][126][127][128] In this regard, it has been reported that mutants of S. coelicolor resistant to the nonutilizable glucose analog, 2-deoxyglucose (DOG), appear to be generally deficient in glucose repression.…”

“…[125][126][127][128] In this regard, it has been reported that mutants of S. coelicolor resistant to the nonutilizable glucose analog, 2-deoxyglucose (DOG), appear to be generally deficient in glucose repression. 122 These mutants (Dog R ) can utilize glycerol, arabinose, fructose and galactose in the presence of glucose. Of these mutants, 85% cannot grow on glucose.…”

“…For instance, it has been previously shown in S. coelicolor that resistance to DOG yields Dog R mutants with decreased glucose kinase activity and reversal of glucose repression. 122 A derivative of the temperate phage jC31 containing glkA alone is not enough to completely restore the wild-type phenotype when used to lysogenize a S. coelicolor glk null mutant with the Dog R phenotype. Complete restoration to the wild-type phenotype is observed with the temperate phage jC31 KC896 containing both glkA and sco2127 genes.…”

Pigmented antibiotic production by Streptomyces coelicolor A3(2): kinetics and the influence of nutrients

“…Hodgson (1982) used both genetical and physiological techniques to investigate glucose uptake and metabolism by S . coelicolor.…”