Health & Environmental Research Online (HERO)


Print Feedback Export to File
4084765 
Journal Article 
Cleaner production of phenylacetylcarbinol by yeast through productivity improvements and waste minimisation 
Oliver, AL; Roddick, FA; Anderson, BN 
1997 
1 
Pure and Applied Chemistry
ISSN: 0033-4545
EISSN: 1365-3075 
Walter de Gruyter GmbH 
69 
11 
2371-2385 
English 
WOS:A1997YF44600021 
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 byproduct 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 fermentation broth 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.