Carbon Catabolite Repression Regulates the Production of the Unique Volatile Sodorifen of Serratia plymuthica 4Rx13

Abstract

Microorganisms are capable of synthesizing a plethora of secondary metabolites including the long-overlooked volatile organic compounds. Little knowledge has been accumulated regarding the regulation of the biosynthesis of such mVOCs. The emission of the unique compound sodorifen of Serratia plymuthica isolates was significantly reduced in minimal medium with glucose, while succinate elevated sodorifen release. The hypothesis of carbon catabolite repression (CCR) acting as a major control entity on the synthesis of mVOCs was proven by genetic evidence. Central components of the typical CCR of Gram-negative bacteria such as the adenylate cyclase (CYA), the cAMP binding receptor protein (CRP), and the catabolite responsive element (CRE) were removed by insertional mutagenesis. CYA, CRP, CRE1 mutants revealed a lower sodorifen release. Moreover, the emission potential of other S. plymuthica isolates was also evaluated.

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.…”

Volatilomes of Bacterial Infections in Humans

“…Alternatively, clarifying the regulation of the biosynthesis of mVOCs will also contribute to this general understanding. Presently, not much work has been performed in this regard, but principal regulatory mechanisms such as quorum sensing and catabolite repression turn out to be involved, as shown for the biosynthesis of schleiferon (Lemfack et al, 2016) and sodorifen (Magnus et al, 2017), just to name two examples.…”

Direct pathway cloning of the sodorifen biosynthetic gene cluster and recombinant generation of its product in E. coli

“…Interestingly, we found that cultivation in TB resulted in slightly higher sodorifen emission, which might solely be a consequence of higher growth rates and cell densities compared to the minimal succDMM medium. As neither TB nor succDMM contain glucose, the carbon catabolite repression system regulating the sod BGC, as described by Magnus et al [14], does not come into effect. Most importantly, all production experiments with the natural producer S. plymuthica WS3236 only resulted in small amounts of sodorifen relative to other VOCs produced.…”

“…Most S. plymuthica strains investigated so far emit a complex mixture of different VOCs mainly at very low concentrations [4], greatly hampering the efficient production for functional screening of individual compounds such as sodorifen. Sodorifen production can be triggered to some extend by co-cultivating S. plymuthica with the fungal pathogen Fusarium culmorum [12] and is furthermore regulated by the carbon catabolite repression system [14]. Different isolates of S. plymuthica exhibit surprisingly variable amounts of sodorifen emission, ranging from < 0.1 to 50% of the total VOC spectrum under identical fermentation conditions [14].…”

“…Sodorifen production can be triggered to some extend by co-cultivating S. plymuthica with the fungal pathogen Fusarium culmorum [12] and is furthermore regulated by the carbon catabolite repression system [14]. Different isolates of S. plymuthica exhibit surprisingly variable amounts of sodorifen emission, ranging from < 0.1 to 50% of the total VOC spectrum under identical fermentation conditions [14]. Given the rather low titers of sodorifen in all natural producers, its inherent volatility and the observed complexity of VOC mixtures obtained by fermentation of S. plymuthica , studies on the functional role of this intriguing metabolite have so far been impeded.…”