CLEANER PRODUCTION OF PHENYLACETYLCARBINOL BY YEAST THROUGH PRODUCTIVITY IMPROVEMENTS AND WASTE MINIMIZATION

Phenylacetylcarbinol (PAC) in its laevo-rotatory chiral form (L-PAC) i s a precursor for the synthesis of L-ephedrine and D-pseudoephedrine, two pharmaceuticals with nasal decongestant properties. L-PAC is gener ated biologically through the pyruvate decarboxylase (PDC)-mediated co ndensation of added benzaldehyde with acetaldehyde generated metabolic ally from feedstock sugars via pyruvate. Some of the added benzaldehyd e is converted through the action of alcohol dehydrogenase(s) to benzy l alcohol, an undesired by-product. L-PAC extracted from the fermentat ion 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 enhan ce the ratio of product to byproduct generated and to minimise the was te treatment burden of the spent fermentation broth. Benzaldehyde deli very to the fermentation has been modified to ensure that sufficient r aw material is available, together with pyruvate, during peak periods of PDC activity, and that benzaldehyde is less available during period s of high alcohol dehydrogenase activity. The inorganic content of the spent fermentation broth has been reduced substantially by the partia l substitution of raw sugar for molasses in the medium, with a reducti on of molasses content by 60% resulting in an increase of PAC yield of 20% and increased specific productivity. Whilst using the raw sugar-m olasses medium we have re-evaluated the contribution of other impure f ermentation feedstocks such as dried whey, and corn steep liquor, and found that both can be eliminated without losses in PAC production. Fu rther 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 gen eration, resulting in an L-PAC process which is considerably ''cleaner '' than the parent process.