[SCAN] CDP-inositol: the exquisite inositol donor for the synthesis of thermoprotectors and phospholipids in prokaryotes

SCAN

Title: CDP-inositol: the exquisite inositol donor for the synthesis of thermoprotectors and phospholipids in prokaryotes

Speaker: Carla Jorge

Affiliation: Helena Santos Lab

Abstract:

CDP-inositol is the donor of inositol-phosphate for the synthesis of di-myo-inositol-phosphate (DIP), and for many years no other function was ascribed to such metabolite. DIP and derivatives have been encountered in members of nearly all marine hyperthermophiles, both Bacteria and Archaea, and also in a few thermophiles. In general, the levels of DIP increase in response to heat stress, leading to the assumption that this solute plays a role in the thermoprotection of cellular components.

The pathway for DIP biosynthesis was established by our group [1]; it involves two consecutive reactions catalysed by L-myo-inositol-1-phosphate cytidylyltransferase (IPCT) and di-myo-inositol phosphate phosphate synthase (DIPPS). The first enzyme catalyses the synthesis of CDP-inositol from L-myo-inositol-1-phosphate and CTP, while the second activity uses CDP-inositol and another molecule of L-myo-inositol-1-phosphate to yield the phosphorylated form of DIP, i.e., DIPP. Dephosphorylation of this intermediate into DIP is catalysed by a yet unknown phosphatase. All organisms known to accumulate DIP possess homologues of IPCT and DIPPS genes, either separated or fused in a single gene product [2]. Surprisingly, we detected the presence of a gene for the synthesis of CDP-inositol in Rhodothermus marinus, a thermophilic bacterium that does not accumulate DIP. The function of the gene coding for IPCT was confirmed by expression in Escherichia coli, and the fate of CDP-inositol in R. marinus was investigated. This work led us to the discovery of a novel pathway for the synthesis of ether-linked inositol phospholipids, which uses CDP-inositol and dialkylether glycerol as substrates [3]. This is unlike all known pathways that involve activation of the lipid moiety instead of the polar head (inositol). Interestingly, the occurrence of ether-linked inositol phospholipids, typical of the domain Archaea, is rare within the domain Bacteria and had never been demonstrated before in R. marinus.

[1] Rodrigues MV, Borges N, Henriques M, Lamosa P, Ventura R, Fernandes C, Empadinhas N, Maycock C, da Costa MS and Santos H (2007) Bifunctional CTP:inositol-1-phosphate cytidylyltransferase/CDP-inositol:inositol-1-phosphate transferase, the key enzyme for di-myo-inositol-phosphate synthesis in several (hyper)thermophiles. J Bacteriol 189:5405-5412.

[2] Gonçalves LG, Borges N, Serra F, Fernandes PL, Dopazo H and Santos H (2012) Evolution of the biosynthesis of di-myo-inositol phosphate, a marker of adaptation to hot marine environments. Environ Microbiol 14: 691-701.

[3] Jorge CD, Borges N, Santos H (2015) A novel pathway for the synthesis of inositol phospholipids uses cytidine diphosphate (CDP)-inositol as donor of the polar head group. Environ Microbiol 17:2492-2504.