Invited Presentation: Tandem Catalysis: From Biosynthesis to Biocatalysis

Tandem or sequential catalysis is a hallmark of natural product biosynthesis in which a series of enzymes act together to convert a simple precursor metabolite to a structurally complex product. In contrast, biocatalysis typically involves single enzymes and single-step transformations. In recent years, there is a growing trend to explore the principle of tandem catalysis for biocatalysis. In this presentation, I will first discuss our recent work on the discovery and engineering of natural product biosynthetic pathways for drug discovery and development (1) and then discuss our attempts to develop tandem catalytic processes that combine biocatalysts (enzymes or engineered whole cells) with chemical catalysts with an ultimate goal of exploring the synergy among different types of catalysis (2,3).

1. Y. Luo, H. Huang, J. Liang, M. Wang, L. Lu, Z. Shao, R. Cobb, and H. Zhao. “Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster.” Nature Communications, 4: 2894 (2013).
2. C. A. Denard, J. Hartwig, and H. Zhao. “Multistep one-pot reactions combining biocatalysts and chemical catalysts for asymmetric synthesis.” ACS Catalysis, 3, 2856−2864 (2013).
3. C. Denard, H. Huang, M. J. Bartlett, L. Lu, Y. Tan, H. Zhao, and J.F. Hartwig. “Cooperative Tandem Catalysis by an Organometallic Complex and a Metalloenzyme.” Angewandte Chemie, 53, 465-469 (2014).