Aerobic nicotinate degradation through 2,5-dihydroxypyridine

A six-reaction aerobic nicotinate degradation route in Pseudomonadota, converting nicotinate to fumarate through 6-hydroxynicotinate, 2,5-dihydroxypyridine, N-formylmaleamate, maleamate and maleate. The characterized two-component NicAB enzyme initiates hydroxylation, followed by NicC oxidative decarboxylation, NicX ring cleavage, NicD deformylation, NicF deamidation and MaiA isomerization. Related bacteria share downstream chemistry while differing in pathway distribution and entry-enzyme architecture.

The complete native route is anchored in Pseudomonas putida KT2440. The taxon is an evidence-supported envelope, not a universal trait or a claim of evolutionary origin. Bordetella bronchiseptica NicC and NicX extend reaction-level sampling to Burkholderiales, but the full Bordetella entry complex is not asserted to have the two-component KT2440 architecture. BB1776 and BB1783 are separately reviewed architectural comparators; their NicB1/NicB2 roles remain predicted. All six reactions are required at this boundary. Nicotinate uptake, cofactor assembly, regulation by NicR/BpsR or NicS, terminal cytochrome oxidation and downstream fumarate metabolism remain context. Nicotine is a different starting substrate: S16 Iso/MaiA is a directly assayed terminal-reaction comparator, not a native complete-route exemplar. PANTHER names are copied verbatim and used only with reaction-specific constraints; no substrate specificity or PAINT ancestral placement is inferred from a family label. All seven PANTHER families of the member proteins have family reviews under interpro/panther/. PANTHER subfamily ids are asserted only where the subfamily corresponds to the role: PTHR44379:SF6 (NicA), PTHR47495:SF1 (NicB) and PTHR34448:SF1 (NicX). They are omitted for NicC, NicD, NicF and MaiA. NicC is split across PTHR13789:SF309 and SF318; PTHR43798:SF33 and PTHR43540:SF1 each mix unrelated hydrolase activities; and PTHR40267:SF1, the only subfamily of its family, combines maleate isomerases with arylmalonate decarboxylase. These four roles are grounded by representative members and the required reaction only. No narrower NCBIfam or InterPro family is used for NicC, NicD or NicF because none is reaction-specific. The MaiA IPR028615 maleate-isomerase signature is cited as reaction evidence. The scope is CONCRETE and lineage-bounded: the complete six-reaction route is experimentally supported only in Pseudomonadota (Pseudomonas and Bordetella). Shared lower-pathway enzymes elsewhere, such as the nicotine-degrading S16 genes, do not establish the full route, so the module is not generalized beyond that phylum. GO lacks exact terms for the NicAB cytochrome reaction and the two amide hydrolases; these leaves use explicit activity names and Rhea chemistry instead of overbroad molecular functions. Gene reviews propose matching new terms. Evidence coverage remains uneven: the founding paper assigns KT2440 MaiA by homology rather than a target enzyme assay, and the reported Bordetella NicX product analysis is a meeting abstract. These are limits of available evidence, not established absence of biochemical knowledge.