In enzymology, a tetrahydrofolate synthase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are ATP, tetrahydropteroyl-[gamma-Glu]n, and L-glutamate, whereas its 3 products are ADP, phosphate, and tetrahydropteroyl-[gamma-Glu]n+1.
This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds as acid-D-amino-acid ligases (peptide synthases). The systematic name of this enzyme class is tetrahydropteroyl-gamma-polyglutamate:L-glutamate gamma-ligase (ADP-forming). This enzyme participates in folate biosynthesis.
As of late 2007, 7 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , and .