Cell-free synthetic biology for biosynthesis of pharmaceutical natural products.

Natural products with significant biological activities continuously act as rich sources for drug discovery and development. To harness the potential of these valuable compounds, robust methods need to be developed for their rapid and sustainable production. Cell-free biosynthesis of pharmaceutical natural products by reconstruction of the entire biosynthetic pathways represents one such solution. In this review, we focus on biosynthesis of two important classes of natural products, polyketides (PKs) and nonribosomal peptides (NRPs). First, we summarize purified enzyme-based systems for the biosynthesis of PKs, NRPs, and PK/NRP hybrids. Then, we introduce the cell-free protein synthesis (CFPS)-based technology for natural product production. With that, we discuss challenges and opportunities of cell-free synthetic biology for biosynthesis of natural products.