Unusual Enzyme Reactions in Natural Product Biosynthesis

b-Nicotinamide adenine dinucleotide (b-NAD) is a pivotal metabolite for all living organisms and functions as a diffusible electron acceptor and carrier in the catabolic arms of metabolism. Furthermore, b-NAD is involved in diverse epigenetic, immunological, and stress-associated processes, where it is known to be sacrificially utilized as an ADP-ribosyl donor for protein and DNA modifications, or the generation of cell-signaling molecules. Here, we report the function of b-NAD in secondary metabolite biosynthetic pathways, in which the nicotinamide dinucleotide framework is heavily decorated and serves as a building block for the assembly of a novel class of natural products. The gatekeeping enzyme of the discovered pathway (SbzP) hereby catalyzes a sophisticated, pyridoxal phosphate (PLP)-dependent (3+2)-annulation reaction between b-NAD and S-adenosylmethionine (SAM), generating a 6-azatetrahydroindane scaffold. Members of this novel family of b-NAD-tailoring enzymes are widely distributed in the bacterial kingdom and encoded in diverse biosynthetic gene clusters. The findings of this work set the stage for the discovery and exploitation of b-NAD-derived natural products.

About the speaker:

Ikuro Abe currently serves as Professor Emeritus at the University of Tokyo, Professor at the Institute of Natural Medicine, University of Toyama, Japan, Visiting Chair Professor at the College of Marine Sciences, National Sun Yat-sen University, Taiwan (2026–), and Gledden Visiting Fellow, University of Western Australia, Australia (2026). Prior to these appointments, he was Professor at the Graduate School of Pharmaceutical Sciences, the University of Tokyo (2009–2026). In recognition of his achievements, he has received numerous prestigious distinctions, including Prizes for Science and Technology by the MEXT Japan (2019) and Medal with Purple Ribbon, Cabinet Office, Government of Japan (2025).

Professor Abe is currently visiting under a UWA Institute of Advanced Studies (IAS) Gledden Visiting Fellowship.