Recent advances in applying cell-free systems for high-value and complex natural product biosynthesis

Natural products have complex chemical structures and exhibit diverse bioactivities. To harness these high-value natural compounds, robust approaches are required for their rapid and sustainable production. Recently, cell-free systems as one promising solution have been applied to produce natural products by reconstitution of their entire biosynthetic pathways in vitro. Here, we highlight recent advances in cell-free biosynthesis of natural products and discuss future challenges and opportunities. We envision that cell-free technology holds tremendous potential for natural product research such as high-throughput screening of peptide-based natural product analogs/variants, expression of toxic metabolic pathways, characterization of enzyme functions, and activation of silent biosynthetic gene clusters.