Industrial biocatalysis

  • date_range Published

    01/11/2018

  • person Written by

    SPILLOproject team

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    162 times



Industrial biocatalysis

by SPILLOproject team

  • visibility Read 162 times


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    Application of SPILLO-PBSS to industrial biocatalysis

    Researchers can find in SPILLO-PBSS a precious ally in detecting the origin of undesired effects regarding enzymes of interest to the industry, as it helps to optimize the use of biological catalysts in industrial processing. Here below is an example for the application of SPILLO-PBSS to a typical problem of industrial interest.

    A Substrate Inhibition Problem


    OBJECTIVE

    The plan was aimed at developing a new industrial process (alternative to chemical synthesis) based on the enzymatic reduction of bile acids, their salts or derivatives, to generate therapeutic agents.                                                                                                                

                                                                                           

     

    THE PROBLEM

    A good catalytic efficiency of the selected enzyme was originally obtained only at laboratory level. Under industrial conditions (at higher concentrations of the substrate), however, an unwanted phenomenon of substrate inhibition appeared, due to unknown causes.


    THE ROLE OF SPILLO-PBSS

    SPILLO-PBSS was used in looking for possible secondary binding sites for the substrate within the enzyme 3D-structure (obtained by modeling). 

     

                                                                        

     

    A previously unknown hidden binding site was identified by SPILLO-PBSS, despite its closed and apparently inaccessible conformational state. 

     

                                                                        

     

    The newly discovered substrate (in YELLOW) binding site turned out to partially overlap to the binding site of the NADPH cofactor (in RED) which, in turn, is necessary for the reaction to take place. Thus, it was possible to hypothesize a sort of competition between the substrate and the cofactor as a probable cause of the substrate inhibition. Such hypothesis was proved on trial.                                                                             

     

    THE SOLUTION

    Understanding the mechanisms which inactivated the enzyme has enabled the design of a suitable strategy in dealing with the substrate inhibition problem, which eventually led to the development and patenting of a new industrial process.