Cell-Free Platform for Natural Product Discovery

The discovery process for natural products is often hindered by time consuming operations including strain engineering and tuning of genetic regulation. Here, we present a platform for the high-throughput discovery of natural products. Cell-free transcription and translation systems allow for the simultaneous evaluation of several genetic architectures within a context that is largely divorced from host metabolic and regulatory processes. As a proof of concept, this platform is used to produce the ribosomally synthesized and post-translationally modified peptide patellamide.