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Cleaner production of phenylacetylcarbinol by yeast through productivity improvements and waste mini

Cleaner production of phenylacetylcarbinol by yeast through productivity improvements and waste mini

  1. thundercles
    Abstract: Phenylacetylcarbinol (PAC) in its laevo-rotatory chiral form (L-PAC) is
    a precursor for the synthesis of L-ephedrine and D-pseudoephedrine, two
    pharmaceuticals with nasal decongestant properties. L-PAC is generated
    biologically through the pyruvate decarboxylase (PDC)-mediated condensation of
    added benzaldehyde with acetaldehyde generated metabolically from feedstock
    sugars via pyruvate. Some of the added benzaldehyde is converted through the
    action of alcohol dehydrogenase(s)to benzyl alcohol, an undesired by-product. L-
    PAC extracted from the fermentation broth is converted chemically by
    hydroamination in the presence of methylamine and hydrogen to L-ephedrine, and
    then by isomerisation to D-pseudoephedrine.
    We have employed a dual approach strategy to enhance the ratio of product to by-
    product generated and to minimise the waste treatment burden of the spent
    fermentation broth. Benzaldehyde delivery to the fermentation has been modified
    to ensure that sufficient raw material is available, together with pyruvate, during
    peak periods of PDC activity, and that benzaldehyde is less available during periods
    of high alcohol dehydrogenase activity. The inorganic content of the spent
    fermentationbroth has been reduced substantially by the partial substitution of raw
    sugar for molasses in the medium, with a reduction of molasses content by 60%
    resulting in an increase of PAC yield of 20% and increased specific productivity.
    Whilst using the raw sugar-molasses medium we have re-evaluated the contribution
    of other impure fermentation feedstocks such as dried whey, and corn steep liquor,
    and found that both can be eliminated without losses in PAC production. Further
    work on the optimisation of the concentrations of carbohydrate, nitrogen and
    phosphate in the fermentation has been conducted and has led to further
    productivity increases, together with reduced waste generation, resulting in an L-
    PAC process which is considerably "cleaner" than the parent process.