Project Grant 2420683

The National Science Foundation (NSF) Division of Chemistry awarded a $594,870 Project Grant to the University of Texas at Austin under the Mathematical and Physical Sciences (CFDA 47.049) program. The grant supports research by Dr. Yi Lu studying how the secondary coordination sphere, the non-binding environment around copper (Cu) enzymes, affects their catalytic activity. The research aims to enhance fundamental knowledge of metal biochemistry and enable practical applications in biocatalysis for sustainable energy and artificial nitric oxide storage/transportation systems. The project employs novel biosynthetic techniques, including the use of unnatural amino acids and loop-directed mutagenesis, to modulate Cu enzyme activity. Key areas of focus include: 1) tuning the reduction potential of a small laccase enzyme to improve oxygen reduction and lignin degradation, 2) controlling polysaccharide degradation by designing a Cu-histidine-brace center in azurin, and 3) regulating reversible S-nitrosylation and trans-nitrosylation between enzymes and small molecules in azurin. The findings could advance understanding of how the secondary coordination sphere environment can be manipulated to enhance the catalytic reactivity of Cu enzymes.