2-hydroxy-3-oxoadipate synthase (HOAS)

2-hydroxy-3-oxoadipate synthase (EC 2.2.1.5) is a thiamine diphosphate-dependent enzyme that catalyzes the condensation of glyoxylate and 2-oxoglutarate to form 2-hydroxy-3-oxoadipate [1]. This enzyme is a key component of the glyoxylate and dicarboxylate metabolism pathway, providing a mechanism for glyoxylate detoxification and metabolic integration [3]. In pathogenic bacteria such as Mycobacterium tuberculosis, it is considered a potential therapeutic target because of its role in maintaining metabolic homeostasis during infection [4]. In humans, this specific carboligase activity is primarily mediated by the E1 subunit of the 2-oxoglutarate dehydrogenase complex (OGDC), an essential part of the tricarboxylic acid (TCA) cycle [2]. Consequently, drug discovery efforts targeting the bacterial enzyme must achieve high selectivity to prevent the inhibition of the human OGDC, which would lead to severe systemic toxicity [2]. While no drugs are currently approved for this target, it remains an area of active research for novel antimicrobial strategies and the management of metabolic conditions involving glyoxylate [4].

Other names

alpha-ketoglutarate-glyoxylate carboligase2-hydroxy-3-oxoadipate glyoxylate-lyase (carboxylating)Glyoxylate-oxoglutarate carboligase2-oxoglutarate-glyoxylate carboligase

Inhibition of the carboligase activity to disrupt glyoxylate processing and bacterial metabolic homeostasis.