Polyketide

Polyketides are produced in bacteria, fungi, plants, and certain marine animals (can be macrolides, macrocycle, cyclic peptides, tetracycline anthracycline, aflatoxin). The biosynthesis involves stepwise condensation of acetyl-CoA or propionyl-CoA with either malonyl-CoA or methylmalonyl-CoA. Polyketides are synthesized by multienzyme polypeptides that resemble eukaryotic fatty acid synthase but are often much larger (called polyketide synthases PKS). They include acyl-carrier domains plus an assortment of enzymatic units that can function in an iterative fashion, repeating the same elongation/modification steps (as in fatty acid synthesis), or in a sequential fashion so as to generate more heterogeneous types of polyketides. The last reaction is often performed by a thioesterase which is an alpha/beta hydrolase. There are various subclasses of polyketides including: aromatics, macrolactones/macrolides, decalin ring containing, polyether, and polyenes. Polyketide synthases are divided into three classes: Type I PKSs (multimodular megasynthases that are non-iterative, often producing macrolides, polyethers, and polyenes), Type II PKSs (dissociated enzymes with iterative action, often producing aromatics), and Type III PKSs (chalcone synthase-like, producing small aromatic molecules). In addition to these subclasses, there also exist polyketides that are hybridized with nonribosomal peptides (Hybrid NRP-PK and PK-NRP). Since nonribosomal peptide assembly lines use carrier proteins similar to those used in polyketide synthases, convergence of the two systems evolved to form hybrids, resulting in polypeptides with nitrogen in the skeletal structure and complex function groups similar to those found in amino acids