The Prodigal Compound: Return of Ribosyl 1,5-Bisphosphate as an Important Player in Metabolism

TY - JOUR

T1 - The Prodigal Compound

T2 - Return of Ribosyl 1,5-Bisphosphate as an Important Player in Metabolism

AU - Hove-Jensen, Bjarne

AU - Brodersen, Ditlev E

AU - Manav, Cemre

N1 - Copyright © 2018 American Society for Microbiology.

PY - 2019/3

Y1 - 2019/3

N2 - Ribosyl 1,5-bisphosphate (PRibP) was discovered 65 years ago and was believed to be an important intermediate in ribonucleotide metabolism, a role immediately taken over by its "big brother" phosphoribosyldiphosphate. Only recently has PRibP come back into focus as an important player in the metabolism of ribonucleotides with the discovery of the pentose bisphosphate pathway that comprises, among others, the intermediates PRibP and ribulose 1,5-bisphosphate (cf. ribose 5-phosphate and ribulose 5-phosphate of the pentose phosphate pathway). Enzymes of several pathways produce and utilize PRibP not only in ribonucleotide metabolism but also in the catabolism of phosphonates, i.e., compounds containing a carbon-phosphorus bond. Pathways for PRibP metabolism are found in all three domains of life, most prominently among organisms of the archaeal domain, where they have been identified either experimentally or by bioinformatic analysis within all of the four main taxonomic groups, Euryarchaeota, TACK, DPANN, and Asgard. Advances in molecular genetics of archaea have greatly improved the understanding of the physiology of PRibP metabolism, and reconciliation of molecular enzymology and three-dimensional structure analysis of enzymes producing or utilizing PRibP emphasize the versatility of the compound. Finally, PRibP is also an effector of several metabolic activities in many organisms, including higher organisms such as mammals. In the present review, we describe all aspects of PRibP metabolism, with emphasis on the biochemical, genetic, and physiological aspects of the enzymes that produce or utilize PRibP. The inclusion of high-resolution structures of relevant enzymes that bind PRibP provides evidence for the flexibility and importance of the compound in metabolism.

AB - Ribosyl 1,5-bisphosphate (PRibP) was discovered 65 years ago and was believed to be an important intermediate in ribonucleotide metabolism, a role immediately taken over by its "big brother" phosphoribosyldiphosphate. Only recently has PRibP come back into focus as an important player in the metabolism of ribonucleotides with the discovery of the pentose bisphosphate pathway that comprises, among others, the intermediates PRibP and ribulose 1,5-bisphosphate (cf. ribose 5-phosphate and ribulose 5-phosphate of the pentose phosphate pathway). Enzymes of several pathways produce and utilize PRibP not only in ribonucleotide metabolism but also in the catabolism of phosphonates, i.e., compounds containing a carbon-phosphorus bond. Pathways for PRibP metabolism are found in all three domains of life, most prominently among organisms of the archaeal domain, where they have been identified either experimentally or by bioinformatic analysis within all of the four main taxonomic groups, Euryarchaeota, TACK, DPANN, and Asgard. Advances in molecular genetics of archaea have greatly improved the understanding of the physiology of PRibP metabolism, and reconciliation of molecular enzymology and three-dimensional structure analysis of enzymes producing or utilizing PRibP emphasize the versatility of the compound. Finally, PRibP is also an effector of several metabolic activities in many organisms, including higher organisms such as mammals. In the present review, we describe all aspects of PRibP metabolism, with emphasis on the biochemical, genetic, and physiological aspects of the enzymes that produce or utilize PRibP. The inclusion of high-resolution structures of relevant enzymes that bind PRibP provides evidence for the flexibility and importance of the compound in metabolism.

KW - 5-bisphosphate

KW - Nucleoside catabolism

KW - Nucleotide metabolism

KW - Nudix hydrolase

KW - PRPP

KW - Phosphonate catabolism

KW - Ribose 1

UR - http://www.scopus.com/inward/record.url?scp=85058871647&partnerID=8YFLogxK

U2 - 10.1128/MMBR.00040-18

DO - 10.1128/MMBR.00040-18

M3 - Review

C2 - 30567937

SN - 1092-2172

VL - 83

JO - Microbiology and Molecular Biology Reviews

JF - Microbiology and Molecular Biology Reviews

IS - 1

M1 - e00040-18

ER -