Enzymatic reductions for the chemist

Hollmann, Frank; Arends, Isabel W. C. E.; Holtmann, Dirk

doi:10.1039/c1gc15424a

Cited by 343 publications

(172 citation statements)

References 424 publications

(227 reference statements)

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“…Biocatalysts commonly outperform chemical catalysts with respect to regio-and substrate selectivity and are active under mild, sustainable and aqueous reaction conditions (Arends et al 2007 ;Hatti-Kaul et al 2007 ;Hollmann et al 2011 ;Rozzel 1999 ). Today, enzymatic and whole-cell catalysis has found a broad range of applications, particularly in the production of fine chemicals, pharmaceuticals or agricultural intermediates (Meyer 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Production of halophilic proteins using Haloferax volcanii H1895 in a stirred-tank bioreactor

Strillinger

Grötzinger

Allers

et al. 2015

Appl Microbiol Biotechnol

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The success of biotechnological processes is based on the availability of efficient and highly specific biocatalysts, which can satisfy industrial demands. Extreme and remote environments like the deep brine pools of the Red Sea represent highly interesting habitats for the discovery of novel halophilic and thermophilic enzymes. Haloferax volcanii constitutes a suitable expression system for halophilic enzymes obtained from such brine pools. We developed a batch process for the cultivation of H. volcanii H1895 in controlled stirred-tank bioreactors utilising knockouts of components of the flagella assembly system. The standard medium Hv-YPC was supplemented to reach a higher cell density. Without protein expression, cell dry weight reaches 10 g L . Two halophilic alcohol dehydrogenases were expressed under the control of the tryptophanase promoter p.tna with 16.8 and 3.2 mg g , respectively, at a maximum cell dry weight of 6.5 g L . Protein expression was induced by the addition of L-tryptophan. Investigation of various expression strategies leads to an optimised two-step induction protocol introducing 6 mM L-tryptophan at an OD of 0.4 followed by incubation for 16 h and a second induction step with 3 mM L-tryptophan followed by a final incubation time of 4 h. Compared with the uncontrolled shaker-flask cultivations used until date, dry cell mass concentrations were improved by a factor of more than 5 and cell-specific enzyme activities showed an up to 28-fold increased yield of the heterologous proteins.

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Section: Introductionmentioning

confidence: 99%

Production of halophilic proteins using Haloferax volcanii H1895 in a stirred-tank bioreactor

Strillinger

Grötzinger

Allers

et al. 2015

Appl Microbiol Biotechnol

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“…Historically, ADHs have been the most demanding enzymes for the synthesis of chiral alcohols (Hollmann 2011), however the appearance of other enzymes such as esterases and lipases together with the discovery of their activities in organic media have made that both hydrolases and ADHs remain nowadays as first choices for the production of chiral alcohols.…”

Section: Alcohol Dehydrogenasesmentioning

confidence: 99%

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Albarrán-Velo

González‐Martínez

Gotor‐Fernández

2017

Biocatalysis and Biotransformation

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Biocatalysis is gaining increasing attention in the academic and industrial sector due to the possibility of developing highly stereoselective transformations in a sustainable manner. The creation of stereogenic centers in organic synthesis is not trivial and multiple approaches have been disclosed based on 2 organometallic and organocatalytic methods with the use of day by day more complex catalysts to induce asymmetry in selected transformations. The intrinsic chirality of enzymes makes them powerful tools for the development of stereoselective transformations, catalysing a wide range of chemical reactions due to the high abundance and diversity of enzymes in nature. In addition, the enormous advances in rational design and molecular biology methods have opened up the possibility to create more robust and versatile biocatalysts, which have improved the initial activities displayed by wild-type enzymes. Therefore, their applicability has been widely increased in terms of reaction conditions, substrate specificity, activity and selectivity among others. All these properties have attracted the industrial sector, which has taken advantage of the enzyme selectivities in multiple scenarios. Herein, the focus has been put in recent developments of stereoselective transformations for the synthesis of valuable building blocks towards the production of pharmaceuticals and biologically active natural products.

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“…Alcohol dehydrogenases (ADHs) have been employed for many years in both academic and industrial groups for the asymmetric reduction of prochiral carbonyl groups to optically active secondary alcohols [1,2]. The natural diversity of ADHs has ensured that enzymes encompassing a broad range of catalytic characteristics have been made available for applications.…”

Section: Introductionmentioning

confidence: 99%

Structures of Alcohol Dehydrogenases from Ralstonia and Sphingobium spp. Reveal the Molecular Basis for Their Recognition of ‘Bulky–Bulky’ Ketones

et al. 2013

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Alcohol dehydrogenases (ADHs) are applied in industrial synthetic chemistry for the production of optically active secondary alcohols. However, the substrate spectrum of many ADHs is narrow, and few, for example, are suitable for the reduction of prochiral ketones in which the carbonyl group is bounded by two bulky and/or hydrophobic groups; so-called 'bulky-bulky' ketones. Recently two ADHs, RasADH from Ralstonia sp. DSM 6428, and SyADH from Sphingobium yanoikuyae DSM 6900, have been described, which are distinguished by their ability to accept bulky-bulky ketones as substrates. In order to examine the molecular basis of the recognition of these substrates the structures of the native and NADPH complex of RasADH, and the NADPH complex of SyADH have been determined and refined to resolutions of 1.5, 2.9 and 2.5 Å respectively. The structures reveal hydrophobic active site tunnels near the surface of the enzymes that are well-suited to the recognition of large hydrophobic substrates, as determined by modelling of the bulkybulky substrate n-pentyl phenyl ketone. The structures also reveal the bases for NADPH specificity and (S)-stereoselectivity in each of the biocatalysts for n-pentyl phenyl ketone and related substrates.

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Enzymatic reductions for the chemist

Cited by 343 publications

References 424 publications

Production of halophilic proteins using Haloferax volcanii H1895 in a stirred-tank bioreactor

Production of halophilic proteins using Haloferax volcanii H1895 in a stirred-tank bioreactor

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Structures of Alcohol Dehydrogenases from Ralstonia and Sphingobium spp. Reveal the Molecular Basis for Their Recognition of ‘Bulky–Bulky’ Ketones

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