Harnessing in vitro platforms for natural product research: in vitro driven rational engineering and mining (iDREAM)

Well-known issues amid in vivo research of natural product discovery and overproduction, such as unculturable or unmanipulable microorganisms, labor-intensive experimental cycles, and hidden rate-limiting steps, have hampered relevant investigations. To overcome these long-standing challenges, many researchers are turning toward in vitro platforms, which bypass the complicated cellular machinery and simplify the study of natural products. Here, we summarize the in vitro driven rational engineering and mining (iDREAM) strategy, which harnesses the flexibility and controllability of in vitro systems to rationally overproduce commodity chemicals and efficiently mine novel compounds. The iDREAM strategy promises to make further significant contributions toward both fundamental advances and industrial practices.