2012
DOI: 10.1007/s00253-012-4072-6
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Novel whole-cell biocatalysts with recombinant hydroxysteroid dehydrogenases for the asymmetric reduction of dehydrocholic acid

Abstract: Ursodeoxycholic acid is an important pharmaceutical so far chemically synthesized from cholic acid. Various biocatalytic alternatives have already been discussed with hydroxysteroid dehydrogenases (HSDH) playing a crucial role. Several whole-cell biocatalysts based on a 7α-HSDH-knockout strain of Escherichia coli overexpressing a recently identified 7β-HSDH from Collinsella aerofaciens and a NAD(P)-bispecific formate dehydrogenase mutant from Mycobacterium vaccae for internal cofactor regeneration were designe… Show more

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Cited by 19 publications
(13 citation statements)
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“…In this way, the use of lyophilized whole-cell containing recombinant HSDHs can represent a solution in the reduction of catalyst costs, maintaining a reasonable safety. This approach was followed by Braun et al and Sun et al obtaining the 12-oxo-UDCA with a yield of 99.5% using engineered E. coli cells [ 86 87 ]. In comparison to the systems that employed purified enzymes (see below), this approach allows higher substrate loading (70–100 mM).…”
Section: Reviewmentioning
confidence: 99%
“…In this way, the use of lyophilized whole-cell containing recombinant HSDHs can represent a solution in the reduction of catalyst costs, maintaining a reasonable safety. This approach was followed by Braun et al and Sun et al obtaining the 12-oxo-UDCA with a yield of 99.5% using engineered E. coli cells [ 86 87 ]. In comparison to the systems that employed purified enzymes (see below), this approach allows higher substrate loading (70–100 mM).…”
Section: Reviewmentioning
confidence: 99%
“…Moreover, for each one of these positions, HSDHs usually show a practically absolute stereoselectivity by oxidizing only either the hydroxyl group above (β configuration) or below (α configuration) the plane of the steroid molecule . The reactions catalyzed by HSDHs are reversible, thus these enzymes can be applied in the regioselective reduction of the corresponding keto derivatives as well …”
Section: Introductionmentioning
confidence: 99%
“…For this, extensive screening of microbial diversity, especially from unexplored organic rich sites, is an effective way to obtain novel and efficient isolates showing specificity for substrate of interest and having ability to sustain supply of reduced cofactor for these enzymes. Further, optimization of nutrient supplement and growth conditions could help in achieving desired level of transformation which could make process economically viable and competitive with other processes for "gram" scale production of chiral synthons (Braun et al, 2012).…”
Section: Introductionmentioning
confidence: 99%