Bacterial glycolate and glyoxylate assimilation (glycerate pathway)

A bacterial central-carbon module that converts glycolate and glyoxylate into D-glycerate, which re-enters core carbon metabolism. The core starts with oxidation of glycolate to glyoxylate by the membrane-associated, three-subunit GlcDEF glycolate oxidase/dehydrogenase (FAD-linked GlcD and GlcE plus the iron-sulfur subunit GlcF). Glyoxylate carboligase (Gcl), a thiamine diphosphate enzyme, then condenses two glyoxylate molecules into tartronate semialdehyde with release of carbon dioxide, and tartronate semialdehyde reductase (GlxR) reduces tartronate semialdehyde to D-glycerate with NADH or NADPH. Two accessory steps can feed the core: phosphoglycolate phosphatase supplies glycolate from 2-phosphoglycolate, and hydroxypyruvate isomerase (Hyi) interconverts hydroxypyruvate and tartronate semialdehyde. The pathway is best characterized in Escherichia coli K-12 and Pseudomonas putida KT2440, and the same gene set is found widely in Proteobacteria. Glycerate kinase, the glyoxylate shunt and the eukaryotic photorespiratory C2 cycle lie outside this module.

Taxonomic scope: the GlcDEF plus Gcl/GlxR route (the bacterial glycerate pathway) is characterized genetically and biochemically in Escherichia coli K-12 and is present as the same gene set in Pseudomonas putida KT2440, so both organisms are carried as representative members of every step. The module report also places the route in other Proteobacteria and, as one of three parallel glyoxylate routes, in Synechocystis; no further organism is added here because none has a reviewed gene set in this corpus. The module is kept bacterial: plants and animals oxidize glycolate with a peroxisomal, O2-dependent FMN glycolate oxidase of an unrelated family and route glyoxylate through aminotransferases (photorespiration), so neither the GlcDEF nor the Gcl/GlxR step generalizes to eukaryotes. Boundary: the core is GlcDEF, Gcl and GlxR. Phosphoglycolate phosphatase is optional because its main bacterial source of 2-phosphoglycolate is DNA repair (E. coli Gph) or, in organisms with Rubisco, photorespiration; P. putida KT2440 lacks the Calvin-cycle context, so PP_0416 is housekeeping salvage. PP_1907 and PP_0094 (other HAD phosphatase candidates in the KEGG ppu00630 bucket) are not modelled. Hyi is optional: disrupting E. coli hyi does not stop growth on glyoxylate or glycolate, and Hyi links hydroxypyruvate (from serine or glycerate) to the tartronate-semialdehyde node rather than carrying glyoxylate carbon. In P. putida KT2440 the gcl-hyi-glxR branch is repressed by GclR in wild type and derepressed in ethylene-glycol-adapted strains, so it is genetically present but conditionally active. Glycerate kinase (GlxK/GarK), malate synthase/isocitrate lyase (glyoxylate shunt), catalase, formate dehydrogenase, glycine cleavage and one-carbon folate steps are excluded. Family grounding uses NCBIfam equivalog families for GlcD, GlcF, Gcl, Hyi, GlxR and Gph, and the PANTHER subfamily PTHR11748:SF103 for GlcE (the parent PTHR11748 family is functionally heterogeneous; see its family review).