Identification of the structural function of a novel enzyme that constructs the main scaffold of antibiotics by condensing the coenzymes NAD and SAM

September 3, 2024

The Cryo-electron Microscopy Structure of a Biosynthetic Enzyme Involved in NAD Alkylation Revealed

A research group of the University of Tokyo and the RIKEN CSRS has successfully identified the three-dimensional structure of the unique pyridoxal 5'-phosphate (PLP)-dependent enzyme SbzP, which catalyzes a tandem C–C bond formation, using β-nicotinamide adenine dinucleotide (β-NAD) and S-adenosylmethionine (SAM) as substrates. This was achieved through cryo-electron microscopy structural analysis.

β-NAD is widely known as a coenzyme involved in redox reactions in living organisms, but it is also known to be a substrate for important human biology proteins such as Sirtuin and PARP. Now that the detailed reaction mechanism of the enzyme that alkylates the nicotinamide moiety has been elucidated, it is expected that new bioactive coenzyme compounds will be synthesised in the future through structure-based enzyme engineering.

Original article

Nature Catalysis doi: 10.1038/s41929-024-01221-5

T. Awakawa, T. Mori, L. Barra, Y. Ahmed, R. Ushimaru, Y. Gao, N. Adachi, T. Senda, T. Terada, D. J. Tantillo, I. Abe,

"The structural basis of pyridoxal 5’-phosphate dependent β-NAD alkylating enzymes".

Contact

Takayoshi Awakawa
Team Leader
Plant Lipid Research Team Team