CMP-KDO biosynthesis

A four-reaction pathway that converts the pentose-phosphate intermediate D-ribulose 5-phosphate into CMP-3-deoxy-D-manno-octulosonate (CMP-KDO), the activated donor of the KDO residues that link lipid A to the core oligosaccharide of Gram-negative lipopolysaccharide. An arabinose-5-phosphate isomerase (KdsD, or a paralog such as GutQ) forms D-arabinose 5-phosphate; KDO 8-phosphate synthase (KdsA) condenses it with phosphoenolpyruvate; KDO 8-phosphate phosphatase (KdsC) releases free KDO; and CMP-KDO synthetase (KdsB) activates KDO with CTP. Transfer of KDO to lipid A by WaaA and the separate ADP-heptose pathway are outside the module boundary.

Scope is ABSTRACT: the four reactions and their enzyme families are conserved across lipopolysaccharide-producing Gram-negative bacteria (and KdsA/KdsB homologs also occur in plants), so the module is written species-neutrally with Escherichia coli K-12 as the experimentally characterized exemplar at every step and Pseudomonas putida KT2440 as a second, homology-only exemplar. KT2440 has two KdsA paralogs (KdsA1 and KdsA2, both listed as representatives of the single KdsA step) and two KdsD-subfamily isomerases, KdsD (PP_0957) and PP_1806; PP_1806 is listed under the KdsD-type variant because PANTHER places it in PTHR42745:SF1, but which pathway receives its product has not been tested. The GutQ-type variant is the enterobacterial PTHR42745:SF2 isomerase. Family groundings use the reviewed PANTHER families for the isomerase (PTHR42745:SF1/SF2), KdsA (PTHR21057, a single-subfamily family despite its DAHP-aldolase name) and KdsB (PTHR42866:SF2, which holds bacterial and plant KdsB despite its mitochondrial name; whether its Shewanella Kdo8N-activating members also activate KDO is left unresolved in the family review). The KdsC step is grounded in InterPro IPR010023 instead, because PANTHER PTHR21485 mixes KdsC phosphatases with CMP-sialic acid synthetases in both of its subfamilies and places E. coli and KT2440 KdsC in different subfamilies; the PTHR21485 family review records why. In E. coli the isomerase and phosphatase steps are genetically redundant, whereas KdsA and KdsB are single-copy. KdsB uses KDO and forms CMP-KDO, so its process is CMP-KDO biosynthesis (GO:0033468), not KDO biosynthesis; the PAINT GO:0019294 assertion on the proteobacterial KdsB node is recorded as a source defect in the E. coli kdsB review (KT2440 KdsB has no GO:0019294 row). The CMP-KDO produced here is consumed by the WaaA/KdtA Kdo transfer step of MODULE:lipid_a_raetz_biosynthesis. The broad KEGG ppu00541 map also contains ADP-heptose, dTDP-rhamnose, GDP-mannose and UDP-sugar enzymes, which are not parts of CMP-KDO synthesis. KdsA, KdsC and KdsB are cytosolic by fractionation proteomics in E. coli, so cytosol is asserted on those leaf annotons rather than as module context; no isomerase location is asserted.