2026/02/13 by Svenja Höfmann, Roman Kogay, Christian Schmerling +8 · 2 voices
Medicine · Biochemistry, Genetics and Molecular Biology · #Coagulation, Bradykinin, Polyphosphates, and Angioedema #Sphingolipid Metabolism and Signaling #Parathyroid Disorders and Treatments
paper · pdf · doi:10.1016/j.jbc.2026.111283
Inorganic polyphosphate (polyP), a linear polymer of orthophosphate residues, occurs in all three domains of life and plays key roles in metabolism and regulation. While polyP metabolism has been well studied in bacteria and eukaryotes, studies in archaea have been limited, where the polyphosphate kinases (PPKs) involved in polyP synthesis remained largely uncharacterized. Notably, members of the Crenarchaeota (Thermoproteota) lack homologs of bacterial PPKs. We identify two genes in the crenarchaeal model organism Sulfolobus acidocaldarius , ( saci2019 and saci2020 ), previously annotated as thymidylate kinases, that together encode a heteromeric archaeal PPK ( Sa PPK3). Saci2019 acts as the catalytic subunit (cPPK3), whereas Saci2020 is a regulatory subunit (rPPK3) that enhances activity through oligomerization. Sa PPK3 is reversible but strongly favors polyP-dependent nucleotide kinase activity, forming ATP from ADP and polyP. Kinetic modelling combined with quantitative 31 P NMR showed that polyP synthesis occurred only at high ATP/ADP ratios in the presence of an ATP recycling system, suggesting that Sa PPK3 promotes ATP production from polyP under low energy conditions in vivo . Enzymatic, structural and phylogenetic analyses place Sa PPK3 in a distinct PPK family within the thymidylate kinase superfamily of P-loop kinases. The PPK3 family members show a patchy distribution, being represented mainly in Crenarchaeota of the families Nitrososphaeraceae and Sulfolobaceae , and in a few bacteria. Our findings identify PPK3 as a critical missing link enzyme involved in archaeal polyP metabolism and suggests that polyP, in addition to its function in phosphate storage, serves as an emergency energy buffer.