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Target intelligence / Profile preview
Beta-ketoacyl-acyl carrier protein synthase I (KASI)
- Target
- KASI
- Molecular classification
- Enzyme, Transferase, Acyltransferase, Fatty acid synthase enzyme (component of type II fatty acid synthase pathway)
01
Overview
Beta-ketoacyl-acyl carrier protein synthase I (KASI) is an enzyme involved in fatty acid biosynthesis, functioning within the type II fatty acid synthase (FASII) system in bacteria and plant plastids[2][4]. It catalyzes the condensation of acyl-acyl-carrier protein and malonyl-acyl-carrier protein to form 3-oxoacyl-acyl-carrier protein, CO₂, and free acyl carrier protein, a key step in fatty acid chain elongation[2][3]. KASI belongs to the family of acyltransferase enzymes (EC 2.3.1.41) and plays a critical role in cellular membrane biogenesis and energy storage by enabling the production of fatty acids of various lengths[1][4]. The enzyme is considered an antibacterial drug target because of its essentiality in pathogens like Mycobacterium tuberculosis and Escherichia coli[3]. Inhibition leads to defective cell membrane synthesis, making it relevant for anti-infective strategies[4]. In plants, KASI is essential for normal development, and mutations disrupt growth and fertility[4].
- Other names
- 3-oxoacyl-[acyl carrier protein] synthase IKAS IKASIEC 2.3.1.41
02
Mechanism of action
Inhibition of KASI blocks fatty acid chain elongation by preventing the Claisen condensation between malonyl-acyl carrier protein and the growing fatty acid chain, resulting in impaired synthesis of essential fatty acids and cell membranes
03
Biological functions
Fatty acid biosynthesisCatalysis of fatty acid chain elongationCell growth and development (particularly in plants)Synthesis of cell membranes
04
Disease associations
Infection (the enzyme is essential for fatty acid biosynthesis in bacteria such as Mycobacterium tuberculosis and Escherichia coli, making it a target for antibacterial drug development)Other (disruption in plants leads to developmental abnormalities)
05
Safety considerations
Targeting KASI in pathogens is promising, but in higher organisms (e.g., plants) inhibition may impact growth and developmentPotential off-target effects with non-selective inhibitors due to conservation of fatty acid synthesis pathway enzymes among organisms
06
Interacting drugs
Experimental fatty acid synthase inhibitors (for example, thiolactomycin and cerulenin are known inhibitors of fatty acid synthase enzymes, though specific clinical drugs targeting KASI are not currently in general clinical use)
07
Biomarkers
Null (no established clinical biomarkers; the enzyme itself can be used in research to screen inhibitor efficacy)
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