Browse/search for people

Publication - Dr Colin Lazarus

    Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite

    Citation

    Fisch, K, Bakeer, W, Yakasai, A, Song, Z, Pedrick, J, Wasil, Z, Bailey, A, Lazarus, C, Simpson, T & Cox, R, 2011, ‘Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite’. Journal of the American Chemical Society, vol 133., pp. 16635 - 16641

    Abstract

    The mechanism of programming of iterative
    highly reducing polyketide synthases remains one of the key
    unsolved problems of secondary metabolism. We conducted
    rational domain swaps between the polyketide synthases encoding
    the biosynthesis of the closely related compounds
    tenellin and desmethylbassianin. Expression of the hybrid
    synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation
    pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of
    programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the
    tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.

    Full details in the University publications repository