Carbon Catabolite Regulation of Secondary Metabolite Formation and Morphological Differentiation in Streptomyces coelicolor

Abstract

In the genus Streptomyces, carbon utilization is of significant importance for the expression of genes involved in morphological differentiation and antibiotic production. However, there is little information about the mechanism involved in these effects. In the present work, it was found that glucose exerted a suppressive effect on the Streptomyces coelicolor actinorhodin (Act) and undecylprodigiosin (Red) production, as well as in its morphological differentiation. Accordingly, using a high-density microarray approach in S. coelicolor grown under glucose repression, at early growth stages, a negative effect was exerted on the transcription of genes involved in Act and Red production, when compared with non-repressive conditions. Seven genes of Act and at least ten genes of Red production were down-regulated by glucose. Stronger repression was observed on the initial steps of antibiotics formation. On the contrary, the coelimycin P1 cluster was up-regulated by glucose. Regarding differentiation, no sporulation was observed in the presence of glucose and expression of a set of genes of the bld cascade was repressed as well as chaplins and rodlins genes. Finally, a series of transcriptional regulators involved in both processes were up- or down-regulated by glucose. This is the first global transcriptomic approach performed to understand the molecular basis of the glucose effect on the synthesis of secondary metabolism and differentiation in the genus Streptomyces. The results of this study are opening new avenues for further exploration.

Secondary Metabolites Produced during the Germination of Streptomyces coelicolor

“…Mannitol and glucose exhibited a higher capacity for secondary metabolism when NMMP medium was used and glycerol was shown to have a higher capacity in cases where AM medium was used. Our results also showed that both nutritionally richer media R3 and AM are more suited to germination and the production of secondary metabolites than the minimal NMMP medium, probably due to the presence of Ca 2+ ions (Eaton and Ensign, 1980 ; Lakey et al, 1983 ), L-amino acids (Hirsch and Ensign, 1976b ), or various carbon sources (Romero-Rodriguez et al, 2016 ) in the richer media.…”

Genome Mining Coupled with OSMAC-Based Cultivation Reveal Differential Production of Surugamide A by the Marine Sponge Isolate Streptomyces sp. SM17 When Compared to Its Terrestrial Relative S. albidoflavus J1074

“…Firstly, it appears likely that surugamide A biosynthesis may be regulated, at least in part, by carbon catabolite repression (CCR). Carbon catabolite repression is a well-described regulatory mechanism in bacteria that controls carbon metabolism [79,80,81,82], and which has also been reported to regulate the biosynthesis of secondary metabolites in a number of different bacterial species, including in Streptomyces isolates [83,84,85,86]. While the TSB and the YD media contain glucose and dextrins as carbon sources, respectively; the complex polysaccharide starch is the carbon source in the SYP-NaCl medium.…”

Modulation of Gene Expression in Actinobacteria by Translational Modification of Transcriptional Factors and Secondary Metabolite Biosynthetic Enzymes

“…This mechanism is one of the most conserved ones reported in various bacteria, including actinobacteria. It protects the cells against wasting proteinsynthesizing machinery and controls secondary metabolism (Romero-Rodríguez et al, 2016van Der Heul et al, 2018). In Streptomyces, CCR by glucose appears to be due to both carbohydrate metabolism intermediaries like fructose 1,6-bisphosphate or glucose 6-phosphate (Ramos et al, 2004;Borodina et al, 2008) and the enzyme glucose kinase (Glk) (Angell et al, 1994).…”