Inspired by exciting recent advances in molecule synthesis, the main goals of this Thrust are (1) to validate and test the AI-driven synthesis planning tool AlphaSynthesis (Thrust 1) and the related AI tools for catalyst design and optimization (Thrust 2), and (2) to develop AI-driven tools for end-to-end optimization of entire synthesis plans. We will explore the retrosynthesis platform of AlphaSynthesis (reverse synthesis) to design synthetic routes for manufacturing of the following three target molecules with known functions: C2’epi amphotericin B (a novel potent and non-toxic antifungal drug candidate), artemisinin (a critical antimalaria drug), and Millad NX 8000 (an environmentally advantageous colorless, odorless thermoplastic clarifier for polypropylene). These routes will explore both chemical catalysis and biological catalysis.
The Lead Researchers:
- Saurabh Sinha, Thrust Lead
- Martin Burke
- Scott Denmark
- Jian Peng
- Huimin Zhao
The Current Projects:
- AlphaSynthesis-Enabled Manufacturing of Millad NX8000 - Identify key reaction and conditions that achieve the target objective for yield, selectivity, and efficiency
- AI-Guided Directed Evolution and Manufacturing of C2'epiAmB - Couple cell-free directed evolution workflow with state-of-the-art protein structure prediction and machine learning models to guide and accelerate engineering efforts