Developing BioNavi for Hybrid Retrosynthesis Planning

• Published in: JACS Au 2024-07, Vol.4 (7), p.2492-2502
• Main Authors: Zeng, Tao, Jin, Zhehao, Zheng, Shuangjia, Yu, Tao, Wu, Ruibo
• Format: Article
• Language: English
• ISSN: 2691-3704; 2691-3704
• DOI: 10.1021/jacsau.4c00228

Illuminating synthetic pathways is essential for producing valuable chemicals, such as bioactive molecules. Chemical and biological syntheses are crucial, and their integration often leads to more efficient and sustainable pathways. Despite the rapid development of retrosynthesis models, few of them consider both chemical and biological syntheses, hindering the pathway design for high-value chemicals. Here, we propose BioNavi by innovating multitask learning and reaction templates into the deep learning-driven model to design hybrid synthesis pathways in a more interpretable manner. BioNavi outperforms existing approaches on different data sets, achieving a 75% hit rate in replicating reported biosynthetic pathways and displaying superior ability in designing hybrid synthesis pathways. Additional case studies further illustrate the potential application of BioNavi in a de novo pathway design. The enhanced web server (http://biopathnavi.qmclab.com/bionavi/) simplifies input operations and implements step-by-step exploration according to user experience. We show that BioNavi is a handy navigator for designing synthetic pathways for various chemicals.