Bacterial L-carnitine catabolism through 3-dehydrocarnitine

An aerobic bacterial pathway that converts L-carnitine to glycine betaine through 3-dehydrocarnitine. An NAD-dependent L-carnitine dehydrogenase forms 3-dehydrocarnitine; a beta-keto acid cleavage enzyme (CdhC/BcoG) transfers the trimethylammonio-acetyl (betainyl) group to acetyl-CoA, releasing acetoacetate and forming betainyl-CoA; and a betainyl-CoA thioesterase releases glycine betaine and free CoA. The thioesterase is either a separate hotdog-fold protein (CdhB) or the C-terminal region of a bifunctional dehydrogenase-thioesterase (CdhAB/BcoE-BcoF). Where carnitine is taken up through an ABC importer, the CaiX substrate-binding protein confers carnitine selectivity on the shared CbcWV choline/betaine/carnitine core. The oxygenolytic CntAB route to trimethylamine, anaerobic Cai reduction to gamma-butyrobetaine, compatible-solute retention, acetoacetate activation, and downstream glycine-betaine demethylation are outside this boundary.

Taxonomic scope. The route is experimentally characterized in two classes of Pseudomonadota: Gammaproteobacteria (P. aeruginosa CdhA/CdhC/CdhB with the CaiX-CbcWV importer; P. putida carnitine dehydrogenase) and Alphaproteobacteria (Sinorhizobium meliloti BcoE-BcoF and BcoG). Reviewed UniProt L-carnitine dehydrogenases from Burkholderia, Agrobacterium, Ruegeria, Streptomyces and Bacillales show the dehydrogenase is wider still, but the module context is kept at Pseudomonadota, where the downstream cleavage and thioesterase steps have been shown. KT2440 (Q88R30-Q88R40) remains an orthology exemplar: its LcdH, CdhC and CdhB candidates (Q88R32, Q88R31, Q88R33) are conserved-locus transfers from the characterized P. aeruginosa proteins and have not been assayed directly. In KT2440, Q88R40/Q88R39 form the shared CbcWV core and Q88R30 is the carnitine-selective CaiX component; Q88R38 CbcX is the choline-binding component and is not part of carnitine-specific uptake. Uptake is optional at this boundary: the Cbc/CaiX importer is the characterized Pseudomonas route, and the S. meliloti uptake system was not defined in PMID:30670548, and PMID:19919675 reports that Rhizobiaceae genomes lack CaiX orthologues. Family groundings. PANTHER:PTHR48075 (SF5) also holds 3-hydroxybutyryl-CoA and 3-hydroxyadipyl-CoA dehydrogenases, and PTHR37418:SF2 holds BKACE enzymes with other beta-keto acid substrates, so both family selectors carry a required_function constraint; the family reviews record these subfamilies as functionally heterogeneous. The CbcW and CbcV families (PTHR47737, PTHR43869) are osmolyte-ABC families whose substrate is set by the binding protein, so the carnitine activity is assigned to the complex, not to these families. GO has no exact terms for the CdhC (EC 2.3.1.317, RHEA:47044) or CdhB (EC 3.1.2.33, RHEA:45716) activities; the member gene reviews carry proposed_new_terms, and the module uses the closest parents GO:0016747 and GO:0016289. Those parents are true of the measured reactions rather than ill-fitting, so the member reviews keep them in core_functions.molecular_function with the exact reaction in proposed_new_terms, rather than taking the proposed_molecular_function route that is reserved for activities with no adequate existing parent; when GO creates the two terms, the ids can be swapped in directly.