BioCyc Id	RXN-23585
Mass Balance Status	Balanced.
Direction Note	The reaction direction shown is in accordance with the direction in which it was curated.
EC Number	1.21.98.5 -- tetraether lipid synthase
Enzyme Commission Synonyms	GDGT/MA synthase GDGT/MAS Mj0619 (locus name) tetraether synthase Tes

Enzyme Commission Summary

This archaeal enzyme catalyses a C-C bond formation during the biosynthesis of tetraether lipids. The bond is formed between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT). The enzyme does not distinguish whether the two lipids are connected in antiparallel or parallel geometry, resulting in formation of two forms of the product, which are known as caldarchaeol and isocaldarchaeol, respectively. The enzyme can also form macrocyclic archaeol phospholipids by joining the two lipid tails of a single substrate molecule. Even though the reaction shown here describes phospholipid substrates, the enzyme can also act on glycolipids or lipids that contains mixed types of polar head groups.

The enzyme is a radical SAM enzyme that contains 3 [Fe₄S₄] clusters and one mononuclear rubredoxin-like iron ion, each found in a separate domain. The enzyme uses the 5'-deoxyadenosyl radical to initiate the reaction, which involves the formation of an intermediate bond between the substrate carbon and a sulfur of one of the [Fe₄S₄] clusters. Two radicals are needed per C-C bond formed. The source of the required additional electrons is not known.

Citations: [Zeng22, Lloyd22]