Coenzyme B-12-dependent and independent photoregulation of carotenogenesis across Myxococcales

Light-induced carotenogenesis in Myxococcus xanthus is controlled by the B-12-based CarH repressor and photoreceptor, and by a separate intricate pathway involving singlet oxygen, the B-12-independent CarH paralogue CarA and various other proteins, some eukaryotic-like. Whether other myxobacteria conserve these pathways and undergo photoregulated carotenogenesis is unknown. Here, comparative analyses across 27 Myxococcales genomes identified carotenogenic genes, albeit arranged differently, with carH often in their genomic vicinity, in all three Myxococcales suborders. However, CarA and its associated factors were found exclusively in suborder Cystobacterineae, with carA-carH invariably in tandem in a syntenic carotenogenic operon, except for Cystobacter/Melittangium, which lack CarA but retain all other factors. We experimentally show B-12-mediated photoregulated carotenogenesis in representative myxobacteria, and a remarkably plastic CarH operator design and DNA binding across Myxococcales. Unlike the two characterized CarH from other phyla, which are tetrameric, Cystobacter CarH (the first myxobacterial homologue amenable to analysis in vitro) is a dimer that combines direct CarH-like B-12-based photoregulation with CarA-like DNA binding and inhibition by an antirepressor. This study provides new molecular insights into B-12-dependent photoreceptors. It further establishes the B-12-dependent pathway for photoregulated carotenogenesis as broadly prevalent across myxobacteria and its evolution, exclusively in one suborder, into a parallel complex B-12-independent circuit.

Automated summary

This study investigates the light-induced carotenogenesis in Myxococcus xanthus and explores its regulation mechanisms. The B-12-based CarH repressor and photoreceptor are found to control the carotenogenesis, along with a separate pathway involving singlet oxygen and various other proteins. Comparative analyses across different Myxococcales genomes reveal the conservation of carotenogenic genes and the presence of CarA and its associated factors exclusively in the suborder Cystobacterineae. The study also reveals a plastic CarH operator design and DNA binding across Myxococcales. Overall, this research provides new insights into photoregulated carotenogenesis and establishes its prevalence and evolution in myxobacteria.