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Publication - Professor Adrian Mulholland

    Construction and in vivo assembly of a catalytically proficient and hyperthermostable de novo enzyme


    Watkins, DW, Jenkins, JMX, Grayson, KJ, Wood, N, Steventon, JW, Le Vay, K, Goodwin, MI, Mullen, AS, Bailey, HJ, Crump, MP, MacMillan, F, Mulholland, AJ, Cameron, G, Sessions, RB, Mann, S & Anderson, JLR, 2017, ‘Construction and in vivo assembly of a catalytically proficient and hyperthermostable de novo enzyme’. Nature Communications, vol 8.


    Although catalytic mechanisms in natural enzymes are well understood,
    achieving the diverse palette of reaction chemistries in re-engineered
    native proteins has proved challenging. Wholesale modification of
    natural enzymes is potentially compromised by their intrinsic
    complexity, which often obscures the underlying principles governing
    biocatalytic efficiency. The maquette approach can circumvent this
    complexity by combining a robust de novo designed chassis with a design
    process that avoids atomistic mimicry of natural proteins. Here, we
    apply this method to the construction of a highly efficient,
    promiscuous, and thermostable artificial enzyme that catalyzes a diverse
    array of substrate oxidations coupled to the reduction of H2O2.
    The maquette exhibits kinetics that match and even surpass those of
    certain natural peroxidases, retains its activity at elevated
    temperature and in the presence of organic solvents, and provides a
    simple platform for interrogating catalytic intermediates common to
    natural heme-containing enzymes.

    Full details in the University publications repository