The bacterial catabolism of lignin
The research on bacterial lignin degradation enzymes will yield fundamental insights into important classes of enzymes. The targeted enzymes are important to the global carbon cycle, particularly in forest ecosystems. Related enzymes are implicated in Alzheimer’s, immune function, vision and other processes. On a more general level, the research will provide insights into the function of metals in biological systems, O2-activation and protein structure:function relationships. On a practical level, the research facilitates the engineering of enzymes and bacteria for green chemistry applications. Woody biomass has considerable potential as a sustainable alternative to petroleum as a feedstock for high-value products. Effective lignin-transforming biocatalysts would help develop this potential and contribute to revitalizing a struggling forestry industry.
Chosterol catabolism by M. tuberculosis and its role in pathogenesis
The proposed research should provide major new insights into bacterial steroid metabolism, acetylation networks in prokaryotes, the role of cholesterol catabolism in Mtb pathogenesis, and the catalytic mechanisms of important families of enzymes. It may also help establish a new method for evaluating the mechanisms underlying host-pathogen interactions. Finally, the research may facilitate the development of novel therapeutic strategies to combat TB inducing.
We discovered that M. tuberculosis contains a cholesterol catabolic pathway encoded by ~60 genes. Several of these cholesterol catabolic enzymes are closely related to the pollutant-degrading enzymes that we study. We are using a variety of approaches to understand the mechanism of these enzymes, especially the oxygenases, and to investigate the role of cholesterol catabolism in pathogenesis. Molecular genetic studies, performed in collaboration with researchers at the Albert Einstein College of Medicine, have demonstrated that specific enzymes are essential for the growth of M. tuberculosis on cholesterol. Animal model studies indicate that cholesterol catabolism occurs throughout infection, but appears most important during the chronic phase.