Coordinated regulation of trimethylamine catabolism in abundant marine bacteria

Methylated amines (MAs) are ubiquitous in the marine environment, constituting an important part of the marine dissolved organic nitrogen pool and contributing to the formation of cloud condensation nuclei in the marine atmosphere. The aerobic trimethylamine (TMA) oxidation pathway represents the primary route for TMA utilization in marine environments and has been characterized in the model marine Roseobacter group bacterium Ruegeria pomeroyi DSS-3. However, the regulatory mechanism underlying this pathway has remained unclear. Transcriptome analysis revealed coordinated induction of the entire pathway by all intermediate MAs. We identified a master regulator, TmaR, which is essential for the growth of R. pomeroyi DSS-3 on any MA. TmaR functions as an activator of tdm and its downstream enzymatic genes, and as a mild repressor of tmm. It regulates target gene transcription by directly binding to their promoter regions and responds to further catabolite(s) derived from MMA. Another regulator, TmoR, acts as a strong repressor of tmm by binding to its promoter. The tmaR gene is widely distributed among alpha- and gamma-proteobacteria, and in most cases, it is located within MA catabolic gene clusters. Together, these results identify a master regulator of TMA catabolism in globally abundant marine bacteria.IMPORTANCETrimethylamine (TMA) is a key marine nitrogen source; however, its catabolic regulation remains poorly understood. This study identifies TmaR as the master transcriptional regulator of the TMA catabolic pathway in abundant marine bacteria. TmaR is essential for growth on all methylated amines, directly activating downstream genes' transcription while repressing the initial tmm gene, and responds to downstream MMA catabolite(s). This coordinated regulation enables efficient nitrogen acquisition from mixed methylamine substrates, a common marine scenario. Homologs of TmaR are widespread among marine Alpha- and Gammaproteobacteria, indicating a conserved regulatory strategy for a globally significant biogeochemical process. Our findings provide crucial molecular insight into ocean nitrogen cycling.