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.

Automated summary

Natural products with complex chemical structures and diverse bioactivities can be produced rapidly and sustainably using cell-free systems, which reconstitute their entire biosynthetic pathways in vitro. This technology holds tremendous potential for various applications in natural product research.