polyketidsynthaser

Polyketide synthases (PKSs) are a large class of multi-functional enzymes found in bacteria, fungi, and plants. They are responsible for the biosynthesis of polyketides, a diverse group of secondary metabolites. Polyketides are characterized by a core structure derived from the iterative condensation of small carboxylic acid units, primarily acetyl-CoA and malonyl-CoA, similar to fatty acid biosynthesis. However, PKSs exhibit a remarkable ability to introduce structural variations, leading to a vast array of complex molecules with significant biological activities.

These enzymes operate through a modular system. Each module typically contains a set of catalytic domains responsible for specific steps in the polyketide chain elongation and modification process. Key domains include the acyltransferase (AT), ketosynthase (KS), and acyl carrier protein (ACP). Additional domains like the ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) introduce modifications to the growing polyketide chain, such as reduction of ketone groups, dehydration, and reduction of double bonds. The order of these modules and the specific domains within them dictate the final structure of the polyketide product.

Polyketides synthesized by PKSs have a wide range of applications, including pharmaceuticals. Many antibiotics, antifungals, immunosuppressants, and anticancer agents are polyketides. Examples include erythromycin, tetracycline, rapamycin, and doxorubicin. The study of PKSs is crucial for understanding natural product biosynthesis and for engineering novel bioactive compounds through combinatorial biosynthesis and domain swapping techniques.