Biotransformations on larger scale are mostly limited to cases in which alternative chemical routes lack sufficient chemo-, regio-, or stereoselectivity. Here, we expand the applicability of biocatalysis by combining cheap whole cell catalysts with a microaqueous solvent system. Compared to aqueous systems, this permits manifoldly higher concentrations of hydrophobic substrates while maintaining stereoselectivity. We apply these methods to four different two-step reactions of carboligation and oxidoreduction to obtain 1-phenylpropane-1,2-diol (PPD), a versatile building block for pharmaceuticals, starting from inexpensive aldehyde substrates. By a modular combination of two carboligases and two alcohol dehydrogenases, all four stereoisomers of PPD can be produced in a flexible way. After thorough optimization of each two-step reaction, the resulting processes enabled up to 63 g L–1 product concentration (98% yield), space-time-yields up to 144 g L–1 d–1, and a target isomer content of at least 95%. Despite the use of whole cell catalysts, we did not observe any side product formation of note. In addition, we prove that, by using 1,5-pentandiol as a smart cosubstrate, a very advantageous cofactor regeneration system could be applied.
Stereoselective Two-Step Biocatalysis in Organic Solvent: Toward All Stereoisomers of a 1,2-Diol at High Product Concentrations
† IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany
‡ Piramal Healthcare UK Ltd., Division of Biocatalysis, The Wilton Centre, R345, TS10 4RF Redcar, United Kingdom
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00232
Publication Date (Web): September 19, 2016
Copyright © 2016 American Chemical Society
*E-mail: Do.Rother@fz-juelich.de.
No comments:
Post a Comment