BIOSYNTHESIS OF ISOPRENOID COMPOUNDS

     Isoprenoids are probably the most diverse and largest family of natural products and include many important drugs (e.g. taxol, artemisinin), valuable flavor and fragrance compounds, as well as pigments, antioxidants and steroids. We have chosen carotenoid biosynthesis as an example to demonstrate the feasibility of evolutionary pathway design. Carotenoids have important biological functions in coloration, photosynthesis and as antioxidants. Evidence suggests that carotenoids help prevent cancer and may suppress the growth of tumor cells.

By combining genes from different organisms into new biosynthetic reaction sequences and in vitro evolution of new catalytic functions, we obtained novel biosynthetic pathways in E. coli, which does not make carotenoids naturally,for the synthesis of diverse new carotenoid structures. We also showed that many carotenoid enzymes are catalytically promiscuous and accept substrates other than their natural substrates allowing synthesis of even more diverse structures. Modeling of protein structures of terpenoid enzyme mutants obtained by in vitro evolution provided new insight in their catalytic functions. Recently, we discovered a novel carotenoid enzyme by searching of microbial genome sequences which when combined with our carotenoid pathways in E. coli results in the synthesis novel polar acyclic carotenoids with interesting chromophores.

 

 

  

 

Last updated: November 2005
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