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Research: Biocatalysis
Often the types of inhibitors we design and develop are close analogues of the original cofactor itself. To facilitate the preparation of especially CoA analogues, our group has been studying the use and application of three of the CoA biosynthetic enzymes, namely PanK, PPAT and DPCK, as biocatalysts for the preparation of such analogues. This is made possible by the known promiscuity of these enzymes, which will accept a range of analogues that have been modified in the cysteamine portion of their native substrates. Most recently we have developed a column-based reactor system for the continuous preparation of CoA analogues by immobilizing the CoA biosynthetic enzymes by fusing them to cellulose-binding domains (CBDs).
We are currently also exploring the use of enzymes in the preparation of mycothiol and intermediates of the mycothiol pathway that may aid our studies of the inhibitors related to this cofactor.
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