Ikuro Abe – Unusual enzyme reactions in natural product biosynthesis

Abstract:

13-Nicotinamide adenine dinucleotide ((3-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, 13-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 13-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 13-NAD and S-adenosylmethionine (SAM), generating a 6-azatetrahydroindane scaffold. Members of this novel family of 13-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 13-NAD-derived natural products. [1, 2]

Bio:

Ikuro Abe is Professor of Natural Products Chemistry at Graduate School of Pharmaceutical Sciences, The University of Tokyo (2009-). He received his B.S. (1984) and Ph.D. (1989) from The University of Tokyo. After two years postdoctoral research with Professor Guy Ourisson at the CNRS Institut de Chimie des Substances Naturelles, and mostly with Professor Michel Rohmer at the Ecole Nationale Superieure de Chimie de Mulhouse in France (1989-1991), he moved to the USA to work with Professor Glenn D. Prestwich at the State University of New York at Stony Brook (1991-1996) and then at The University of Utah (1996-1998).

His research interests mostly focus on exploring and engineering the natural products biosynthesis. He has authored 350+ publications, including Nature, Nat Catal, Nat Chem, Nat Chem Biol, Nat Comm, JACS, ACIE, and PNAS. He received the Pharmaceutical Society of Japan Award in 2019, and Prizes for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology, Japan. He is a former President of The Japanese Society of Pharmacognosy.