Bacterial pyruvate oxidation, anaplerosis, and PEP interconversion

A reusable bacterial central-carbon module centered on three direct fates of pyruvate and phosphoenolpyruvate: oxidative conversion of pyruvate to acetyl-CoA by the pyruvate dehydrogenase complex, replenishment of oxaloacetate by pyruvate carboxylase or phosphoenolpyruvate carboxylase, and direct interconversion between phosphoenolpyruvate and pyruvate. The module excludes complete glycolysis, the tricarboxylic acid cycle, lactate and acetate utilization, amino-acid degradation, methylglyoxal detoxification, fatty-acid synthesis, and other reactions included on broad pathway maps.

The module is intentionally narrower than a KEGG pyruvate-metabolism map. Cofactor installation, upstream pyruvate production by complete glycolytic or Entner-Doudoroff routes, downstream acetyl-CoA and oxaloacetate utilization, and substrate-specific routes that merely produce or consume pyruvate are cross-module dependencies. An organism may realize one or more anaplerotic routes and one or both direct PEP/pyruvate directions. The pyruvate dehydrogenase branch is optional because bacteria may instead oxidize pyruvate through enzymes such as pyruvate:ferredoxin oxidoreductase, particularly under anaerobic conditions. The module is species-neutral. Each leaf is grounded in an experimentally characterised exemplar (E. coli AceE, AceF, LpdA, Ppc, PykF and PpsA; B. subtilis PycA; human PC), and every leaf that P. putida KT2440 realises also lists its KT2440 member, which carried the original instance. KT2440 has no single-chain pyruvate carboxylase, so that variant has no KT2440 member. The E3 step is a variant set over two PTHR22912 E3 subfamilies, because the PTHR22912 family review scopes the E3 activity to subfamilies: SF160 (E. coli LpdA, the experimental exemplar) and SF224 (KT2440 LpdG, PP_4187). The earlier KT2440 exemplar Lpd (PP_5366, Q88C17) is an LPD-3 paralog and is no longer listed. Further E3 subfamilies accepted by the family review (SF151, SF217, SF219 and others) can be added as variants when a member is curated for this module. The two pyruvate carboxylase variants cannot be told apart by PANTHER family alone: the two-subunit beta subunit (KT2440 PycB) and single-chain PCs share PTHR43778:SF2, so the two-subunit route is identified by its PTHR48095:SF1 biotin carboxylase partner and the single-chain route by having all three domains on one chain. Single-chain pyruvate carboxylase, two-subunit pyruvate carboxylase and PEP carboxylase are all represented as anaplerotic alternatives.