Abstract
A process for providing intermediate compounds as building blocks for effectively producing statins is described. The presented process is based on acetoxyacetaldehyde and acetaldehyde as substrates, which are presented in an aldol reaction catalyzed by a crude deoxyribose-5-phosphate aldolase (DERA) expressing culture lysate. Different addition regimes of both reactants into a reaction mixture were applied. For the highest concentration of product ((2S,4R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, in the presented crude DERA expressing culture lysate-catalyzed reaction used further in the production of statins, the best addition time of reactants is described. Improved process conditions and reactants’ feeding regime were achieved by converting a batch reaction to a fed-batch process, reaching the highest concentration of product ((2S,4R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl)methyl acetate near 77 g/L. The complete process was designed in a practical and economical manner and could be used further on an industrial scale.
Published Version
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