Recent Advances in Re-engineering Modular PKS and NRPS Assembly Lines

Abstract

Polyketides such as the antibiotic erythromycin or the immunosuppressant rapamycin, and non-ribosomal peptides, such as the antibiotics penicillin or vancomycin, are important classes of natural products. The core of these molecules are biosynthesized by large polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS), respectively. The modular architecture of these enzymatic assembly lines makes them interesting candidates for synthetic biology approaches. The re-engineering efforts aim to understand the molecular structure, produce new compounds, produce analogs of known compounds, tag the products or improve activity and/or yield. Here, we first consider the definition of PKS and NRPS modules, then give an overview of different strategies for re-engineering and finally review recent examples of PKS and NRPS reengineering.