Early steps of tetrahydrofolate and tetrahydromethanopterin
pathways
in Bacteria and Archaea. Most bacteria use the FolE (or FolE2)/FolB/FolK
route (in blue) to 6-HMDP even if some use the bacterial PTPS-III
shunt (in green). Several routes to the common 6-HMDP intermediate
in tetrahydrofolate and tetrahydromethanopterin are found in Archaea.
A common pathway is the FolE2/MptD/MptE route (in red) such as in H. volcanii paralleling the bacterial pathway. However,
some methanogens such as M. jannaschii use the MptA/MptB/MptD/MptE
route, whereas P. furiosus uses the archaeal PTPS-III
shunt. Phosphatases still to be identified are noted by a question
mark (?). FolE/FolE2, GTP cyclohydrolase IA/IB (GCYH-IA/B); FolB,
7,8-dihydroneopterin aldolase (DHNA); FolK, 7,8-dihydro-6-hydroxymethylpterin
diphosphokinase (6-HMDPK); MptA, archaeal GTP cyclohydrolase I (Fe(II)-dependent
enzyme); MptB, Fe(II) dependent-cyclic phosphodiesterase; MptD, archaeal
specific DHNA; MptE, archaeal specific 6-HMDPK; PTPS-III/PTPS-V/PTPS-VI,
pyruvoyltetrahydropterin synthase paralogs involved in 6-HMDP synthesis.