GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Pribat, A, Blaby, IK, Lara-Núñez, A, Gregory, JF 3rd, de Crécy-Lagard, V and Hanson, AD (2010) FolX and FolM are essential for tetrahydromonapterin synthesis in Escherichia coli and Pseudomonas aeruginosa. J. Bacteriol. 192:475-82


Tetrahydromonapterin is a major pterin in Escherichia coli and is hypothesized to be the cofactor for phenylalanine hydroxylase (PhhA) in Pseudomonas aeruginosa, but neither its biosynthetic origin nor its cofactor role has been clearly demonstrated. A comparative genomics analysis implicated the enigmatic folX and folM genes in tetrahydromonapterin synthesis via their phyletic distribution and chromosomal clustering patterns. folX encodes dihydroneopterin triphosphate epimerase, which interconverts dihydroneopterin triphosphate and dihydromonapterin triphosphate. folM encodes an unusual short-chain dehydrogenase/reductase known to have dihydrofolate and dihydrobiopterin reductase activity. The roles of FolX and FolM were tested experimentally first in E. coli, which lacks PhhA and in which the expression of P. aeruginosa PhhA plus the recycling enzyme pterin 4a-carbinolamine dehydratase, PhhB, rescues tyrosine auxotrophy. This rescue was abrogated by deleting folX or folM and restored by expressing the deleted gene from a plasmid. The folX deletion selectively eliminated tetrahydromonapterin production, which far exceeded folate production. Purified FolM showed high, NADPH-dependent dihydromonapterin reductase activity. These results were substantiated in P. aeruginosa by deleting tyrA (making PhhA the sole source of tyrosine) and folX. The DeltatyrA strain was, as expected, prototrophic for tyrosine, whereas the DeltatyrA DeltafolX strain was auxotrophic. As in E. coli, the folX deletant lacked tetrahydromonapterin. Collectively, these data establish that tetrahydromonapterin formation requires both FolX and FolM, that tetrahydromonapterin is the physiological cofactor for PhhA, and that tetrahydromonapterin can outrank folate as an end product of pterin biosynthesis.


PubMed PMC2805310 Online version:10.1128/JB.01198-09


Bacterial Proteins/genetics; Bacterial Proteins/physiology; Computational Biology; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/physiology; Folic Acid/metabolism; Gene Expression Regulation, Bacterial/genetics; Gene Expression Regulation, Bacterial/physiology; Genetic Complementation Test; Models, Genetic; Mutation; Neopterin/genetics; Neopterin/metabolism; Pseudomonas aeruginosa/genetics; Pseudomonas aeruginosa/metabolism; Pterins/metabolism; Racemases and Epimerases/genetics; Racemases and Epimerases/physiology; Tetrahydrofolate Dehydrogenase/genetics; Tetrahydrofolate Dehydrogenase/physiology