TY - JOUR T1 - A GenoChemetic strategy for derivatization of the violacein natural product scaffold JF - bioRxiv DO - 10.1101/202523 SP - 202523 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 Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/29/202523.abstract N2 - 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. ER -