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Scale‐up and intensification of ( S )‐1‐(2‐chlorophenyl)ethanol bioproduction: Economic evaluation of whole cell‐catalyzed reduction of o ‐Chloroacetophenone
Author(s) -
Eixelsberger Thomas,
Woodley John M.,
Nidetzky Bernd,
Kratzer Regina
Publication year - 2013
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.24896
Subject(s) - biotransformation , bioproduction , biocatalysis , alcohol dehydrogenase , bioreactor , chemistry , product inhibition , fermentation , catalysis , formate dehydrogenase , ethanol , ethanol fuel , chromatography , biochemistry , organic chemistry , enzyme , formate , reaction mechanism , non competitive inhibition
Escherichia coli cells co‐expressing genes coding for Candida tenuis xylose reductase and Candida boidinii formate dehydrogenase were used for the bioreduction of o ‐chloroacetophenone with in situ coenzyme recycling. The product, ( S )‐1‐(2‐chlorophenyl)ethanol, is a key chiral intermediate in the synthesis of polo‐like kinase 1 inhibitors, a new class of chemotherapeutic drugs. Production of the alcohol in multi‐gram scale requires intensification and scale‐up of the biocatalyst production, biotransformation, and downstream processing. Cell cultivation in a 6.9‐L bioreactor led to a more than tenfold increase in cell concentration compared to shaken flask cultivation. The resultant cells were used in conversions of 300 mM substrate to ( S )‐1‐(2‐chlorophenyl)ethanol (e.e. >99.9%) in high yield (96%). Results obtained in a reaction volume of 500 mL were identical to biotransformations carried out in 1 mL (analytical) and 15 mL (preparative) scale. Optimization of product isolation based on hexane extraction yielded 86% isolated product. Biotransformation and extraction were accomplished in a stirred tank reactor equipped with pH and temperature control. The developed process lowered production costs by 80% and enabled ( S )‐1‐(2‐chlorophenyl)ethanol production within previously defined economic boundaries. A simple and efficient way to synthesize ( S )‐1‐(2‐chlorophenyl)ethanol in an isolated amount of 20 g product per reaction batch was demonstrated. Biotechnol. Bioeng. 2013; 110: 2311–2315. © 2013 Wiley Periodicals, Inc.