Enzymology of oxidative sulfur transfers
Sulfur containing secondary metabolites are prime modulators of the redox and metal homeostasis in microbial as well as human cells and therefore play important roles in many medical disorders. The identification of novel biothiols and investigation of their biosynthesis physiological functions has gained much interest in the last few years.The enzymology of sulfur incorporation for many of these compounds is not clear and suggesting that much of C-S bond forming biocatalysis is yet to be discovered. In this proposal we focus on a recently discovered class of iron (II) dependent enzymes which affords oxidative sulfur insertion into unactivated C-H bonds. One of these enzymes is responsible for ergothioneine biosynthesis – a 2-thiohistidine derivative which has gained much recent interest due to its potential role in Crohns desease, and in the redox homeostasis in human tissue. We plan to investigate the catalytic mechanism of these enzymes that we termed sulfoxide synthases. Identification of the critical catalytic steps of this unprecedented enzymatic reaction would make important contribution to the general understanding of biocatalysis.
This research is funded by an ERC starting grant.
Biocatalysis for solid substrates
Anaerobic microbial activity combined with geothermal forces transformed prehistoric lignocellulose to fossil fuel. Because this conversion requires millions of years, fossil fuel is not a sustainable resource for our economy. In contrast, aerobic microbes can metabolize cellulose, hemicellulose and lignin at a rate of some 50 billion tons per year. Recruitment of this process may therefore be a key technology to utilize biomass as a sustainable feedstock for the production of fine chemicals or advanced materials and liquid transportation fuel. The principle challenge in this quest is posed by the heterogeneous and solid nature of lignocellulose. Biocatalyst design for solid substrates is mostly unchartered territory but is an exciting frontier for enzyme engineers.
This research is funded by the Swiss National Science Foundation through the National Research Programme 66