PT - JOURNAL ARTICLE AU - Hung-En Lai AU - Alan M. C. Obled AU - Soo Mei Chee AU - Rhodri M. Morgan AU - Sunil V. Sharma AU - Simon J. Moore AU - Karen M. Polizzi AU - Rebecca J. M. Goss AU - Paul S. Freemont TI - A GenoChemetic strategy for derivatization of the violacein natural product scaffold AID - 10.1101/202523 DP - 2019 Jan 01 TA - bioRxiv PG - 202523 4099 - http://biorxiv.org/content/early/2019/01/29/202523.short 4100 - http://biorxiv.org/content/early/2019/01/29/202523.full AB - Integrating synthetic chemistry with synthetic biology allows rapid access to xenobiotic compounds which may provide improved therapeutic activity. By supplementing an Escherichia coli strain expressing the violacein biosynthesis pathway with eight tryptophan substrate analogues or tryptophan halogenase RebH in vivo, 68 new-to-nature analogues of violacein were generated. Furthermore, 20 new derivatives were generated from brominated analogues via Suzuki-Miyaura cross-coupling reaction directly using the crude extract without prior purification. Herein, we demonstrate a flexible and rapid approach to access diverse chemical space that can be applied to a wide range of natural product scaffolds.