Polyketide cyclase

Polyketide cyclases are small enzymes (~140 amino acids in some cases) found in bacteria, fungi, and plants, functioning specifically to catalyze regiospecific and stereospecific ring-closure reactions during the biosynthesis of polyketide natural products[5][3]. These reactions determine the scaffold, complexity, and stereochemistry of drug-like compounds such as anthracycline antibiotics (e.g., doxorubicin, daunorubicin)[5]. Polyketide cyclases act upon linear polyketide intermediates generated by polyketide synthases, folding and cyclizing these chains into the desired multi-ringed structures; product specificity, timing, and the regiospecificity of cyclization are heavily dependent on cyclase action[3]. Members include aromatase/cyclase (ARO/CYC) enzymes such as SnoaL, DnrD, and related proteins from actinomycetes. Their function is pivotal for the industrial and engineered biosynthesis of a broad array of pharmaceutical agents[5][2][7].

Other names

Aromatase/cyclase (ARO/CYC)e.g., DnrDDauDRdmAAknHSnoaL

Catalysis of intramolecular cyclization reactions Control of regiospecific folding/aromatization of polyketide chains[5][3] Acid–base catalysis, without covalent or metal-ion catalysis[5]