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• 1 2020-05-05T23:12:30+00:00 Ahmad Alrusayes 3 plain 2020-05-08T23:50:47+00:00

  
  Engineering a Prenyltransferase Enzyme for Biocatalytic Diversification of Bioactive Compounds

  Overview: Prenyltransferases are enzymes that catalyze the transfer of a prenyl moiety to diverse compounds naturally. Enzymes function as biocatalysis of reactions is essential for the survival of the living systems. In this research, we studied the X-ray crystal structure of one of these prenyltransferases to make it more proficient and promiscuous. 
  
  Abstract: Enzymes serve an important role in any biological system as the biocatalysis of reactions is essential for the survival of the living systems. Under biologically relevant conditions, uncatalyzed reactions tend to be extremely slow and the presence of enzymes catalyze these reactions in a specific and selective manner rapidly. Many chemical reactions require toxic petroleum-derived solvents and extreme reaction conditions which complicate process development and oftentimes create safety hazards to exclude even traces of water from their reaction media. Indeed, enzymes circumvent these problems by providing a specific environment within which a given reaction can occur more rapidly. This inspired chemists to manipulate these natural enzymes to catalyze difficult reactions under favorable reactions of pH, temperature, and green conditions. Furthermore, engineering the active binding sites of enzymes to become more efficient is a hot research area and can lead to the catalysis of challenging chemical reactions. Prenyltransferases (PTs) are important enzymes that catalyze the transfer of a prenyl moiety to diverse compounds naturally. By transferring a prenyl moiety to a compound, the bioactivity of the substance might increase because the hydrophobicity of the substance will increase. This lowers the substance interaction with water in the system and, therefore, the reaction will have higher yield and reproducibility. By engineering PTs to have higher promiscuity, it is possible to use them as unique tools to generate more active compounds. In this project, we will study the X-ray crystal structure of one of these PTs and use mutagenesis to make it more proficient and promiscuous. The enzymes are then screened for their ability to diversify drugs which their counterparts wild type do not perform. A combination of different mutagenesis approaches will be used to enhance the activity of PTs towards nonnative substrates.
  
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