Enzyme-integrated high-throughput Multicomponent synthesis for Echo-enabled Rapid molecule generation and Assay in Lead Discovery

Objective

Indoles are among the most widely encountered scaffolds in medicines and natural products, yet general strategies for their systematic diversification remain limited. Through EMERALD (Enzyme-integrated high-throughput Multicomponent synthesis for Echo enabled Rapid molecule generation and Assay in Lead Discovery), I will unites three complementary techniques into the first miniaturized, automated pipeline for late-stage indole diversification at nanoliter scale (i) multicomponent reactions for efficient and modular assembly of indole frameworks; (ii) enzymatic tailoring, enabling regio- and chemoselective functionalization; and (iii) acoustic droplet ejection combined with real-time mass spectrometry, delivering ultra-high throughput synthesis and analytics with >90% reductions in solvent use. During a secondment at the University of St Andrews, I will evaluate enzyme panels to produce compatibility and selectivity maps directly relevant to drug discovery. Importantly, a subset of the resulting functionalized indoles will be screened against the p53–MDM2 interaction, a clinically validated target in oncology, to demonstrate the platforms’ direct translational potential. By marrying chemical and enzymatic methodologies, EMERALD establishes a sustainable route to novel scaffolds and natural product–inspired analogues, while providing an ideal interdisciplinary training ground at the interface of chemistry, biocatalysis, and automation-ultimately advancing greener drug discovery and fostering my path to research independence.