Lipoic acid synthase (LIAS)

Lipoic acid synthase (LIAS) is a mitochondrially-localized iron–sulfur cluster enzyme essential for the de novo biosynthesis of lipoic acid, a vital cofactor for several mitochondrial enzyme complexes[1][5]. LIAS catalyzes the final step of lipoic acid biosynthesis by inserting two sulfur atoms into the octanoyl moiety of target lysine residues on apoproteins, via a radical S-adenosylmethionine (SAM) dependent mechanism utilizing two distinct [4Fe–4S] clusters[1][2]. The resulting lipoylated enzymes are crucial for core mitochondrial functions, notably oxidative decarboxylation and energy production. Mutations in LIAS impair protein lipoylation, causing metabolic encephalopathies and severe mitochondrial diseases predominantly in childhood[1][3]. LIAS is highly conserved and operates with accessory proteins such as NFU1 for proper Fe–S cluster regeneration and function[2]. It is not a direct drug target, but its activity is indispensable for normal mitochondrial biochemistry.

Other names

Lipoyl synthase, mitochondrialLIASLASHUSSY-01LSLip-synLipoate synthaseHGCLASLIP1PDHLD

Not applicable for direct pharmacological targeting; mechanistically, LIAS catalyzes the sulfur insertion into octanoyl substrates, generating the lipoyl cofactor[1][2][3].