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Organic & biomolecular chemistry

Highly efficient and stereoselective biosynthesis of (2S,5S)-hexanediol with a dehydrogenase from Saccharomyces cerevisiae.


PMID 20237665

Abstract

The enantiopure (2S,5S)-hexanediol serves as a versatile building block for the production of various fine chemicals and pharmaceuticals. For industrial and commercial scale, the diol is currently obtained through bakers' yeast-mediated reduction of 2,5-hexanedione. However, this process suffers from its insufficient space-time yield of about 4 g L(-1) d(-1) (2S,5S)-hexanediol. Thus, a new synthesis route is required that allows for higher volumetric productivity. For this reason, the enzyme which is responsible for 2,5-hexanedione reduction in bakers' yeast was identified after purification to homogeneity and subsequent MALDI-TOF mass spectroscopy analysis. As a result, the dehydrogenase Gre2p was shown to be responsible for the majority of the diketone reduction, by comparison to a Gre2p deletion strain lacking activity towards 2,5-hexanedione. Bioreduction using the recombinant enzyme afforded the (2S,5S)-hexanediol with >99% conversion yield and in >99.9% de and ee. Moreover, the diol was obtained with an unsurpassed high volumetric productivity of 70 g L(-1) d(-1) (2S,5S)-hexanediol. Michaelis-Menten kinetic studies have shown that Gre2p is capable of catalysing both the reduction of 2,5-hexanedione as well as the oxidation of (2S,5S)-hexanediol, but the catalytic efficiency of the reduction is three times higher. Furthermore, the enzyme's ability to reduce other keto-compounds, including further diketones, was studied, revealing that the application can be extended to alpha-diketones and aldehydes.

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