| Autor: |
Bailey SS; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Payne KAP; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Saaret A; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Marshall SA; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Gostimskaya I; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Kosov I; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Fisher K; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK., Hay S; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK. sam.hay@manchester.ac.uk., Leys D; Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK. david.leys@manchester.ac.uk. |
| Abstrakt: |
The UbiD enzyme plays an important role in bacterial ubiquinone (coenzyme Q) biosynthesis. It belongs to a family of reversible decarboxylases that interconvert propenoic or aromatic acids with the corresponding alkenes or aromatic compounds using a prenylated flavin mononucleotide cofactor. This cofactor is suggested to support (de)carboxylation through a reversible 1,3-dipolar cycloaddition process. Here, we report an atomic-level description of the reaction of the UbiD-related ferulic acid decarboxylase with substituted propenoic and propiolic acids (data ranging from 1.01-1.39 Å). The enzyme is only able to couple (de)carboxylation of cinnamic acid-type compounds to reversible 1,3-dipolar cycloaddition, while the formation of dead-end prenylated flavin mononucleotide cycloadducts occurs with distinct propenoic and propiolic acids. The active site imposes considerable strain on covalent intermediates formed with cinnamic and phenylpropiolic acids. Strain reduction through mutagenesis negatively affects catalytic rates with cinnamic acid, indicating a direct link between enzyme-induced strain and catalysis that is supported by computational studies. |
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