The Enzyme Database


Enzyme Nomenclature News

March 2020

Synthases and synthetases

[Prepared by Ron Caspi]

The terms synthase and synthetase, which appear in the accepted names of enzymes, sound similar and have been used interchangeably in the past, yet they have different meanings.

The name synthase is rather generic. Unlike terms such as carboxylase or hydratase, it does not describe a particular type of enzymic activity. All it indicates is that the reaction catalysed by the enzyme is synthetic, rather than catabolic, in nature.

The term is used for different reasons. The most common case is when an enzyme catalyses a complicated transformation that is difficult to define in a concise way. An example for such use is EC, aerobic 5,6-dimethylbenzimidazole synthase. This enzyme catalyses the fragmentation and contraction of a bound reduced flavin mononucleotide (FMNH2) and cleavage of its ribityl tail to form 5,6-dimethylbenzimidazole and D-erythrose 4-phosphate in a reaction that has been described as "cannibalization" [1].

A second case where the term synthase is used is when the enzyme's activity involves two or more reactions of different nature, making it difficult to decide which of the activities should be used for naming the enzyme. For example, EC, tryptophan synthase, catalyses a lyase reaction that splits 1-C-(indol-3-yl)glycerol 3-phosphate into indole and D-glyceraldehyde 3-phosphate, followed by a transfer reaction, transferring the indole to an L-serine, replacing its hydroxyl moiety and forming L-tryptophan.

The third reason to use the term synthase is simply to preserve names that have been used for some time and adapted by the scientific community. Since the term is not incorrect, it is sometime preferable to keep it even though a more precise name is feasible. An example is EC, eugenol synthase, which could have been called by the more precise name coniferyl ester reductase.

In addition to the accepted names, the Enzyme Commission also specifies systematic names that provide a more precise description of the reaction. In the case of the three enzymes mentioned above, the corresponding systematic names are FMNH2 oxidoreductase (5,6-dimethylbenzimidazole-forming); L-serine hydro-lyase [adding 1-C-(indol-3-yl)glycerol 3-phosphate, L-tryptophan and D-glyceraldehyde-3-phosphate-forming]; and eugenol:NADP+ oxidoreductase (coniferyl ester reducing). As is evident, the systematic names are much more complicated in these cases, explaining why the term synthase has been so popular. As of August 2019, 848 Enzyme Commission entries use that term in their accepted name.

The term synthetase, on the other hand, is rather specific. Its proper use has been reserved only for ligases, enzymes that catalyse the joining together of two molecules, powered by the hydrolysis of a diphosphate bond in ATP or a similar triphosphate (classified under class 6). Acknowledging the confusion that the two similar terms have caused, the Enzyme Commission decided in 1983 to abandon the use of the term synthetase for accepted names, replacing it with names of the type X—Y ligase. Most of the names have been subsequently modified to reflect this decision. However, a small number of cases where the reaction is more complex (for example, an intramolecular ligation as in EC, olefin β-lactone synthetase) have retained the term synthetase in their accepted names. As of August 2019, only 7 such entries remain.

1. Taga, M.E., Larsen, N.A., Howard-Jones, A.R., Walsh, C.T. and Walker, G.C. BluB cannibalizes flavin to form the lower ligand of vitamin B12. Nature 446:449 (2007).