Deracemization By Simultaneous Bio‐oxidative Kinetic Resolution and Stereoinversion

Schrittwieser, Joerg H.; Groenendaal, Bas; Resch, Verena; Ghislieri, Diego; Wallner, Silvia; Fischereder, Eva‐Maria; Fuchs, Elisabeth; Grischek, Barbara; Sattler, Johann H.; Macheroux, Peter; Turner, Nicholas J.; Kroutil, Wolfgang

doi:10.1002/anie.201400027

Cited by 73 publications

(55 citation statements)

References 67 publications

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“…The racemic substrates were transformed to optically pure (>97% e.e.) (S)-berbine products with nearly complete conversion (98%) and up to 88% isolated yield (75).…”

Section: Pictet-spengler Cyclisation: Berberine Bridge Enzyme (Bbe)mentioning

confidence: 99%

Biocatalysis: A Status Report

Bommarius

2015

Annu. Rev. Chem. Biomol. Eng.

130

100

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This review describes the status of the fields of biocatalysts and enzymes, as well as existing drawbacks, and recent advances in the areas deemed to represent drawbacks. Although biocatalysts are often highly active and extremely selective, there are still drawbacks associated with biocatalysis as a generally applicable technique: the lack of designability of biocatalysts; their limits of stability; and the insufficient number of well-characterized, ready-to-use biocatalysts. There has been significant progress on the following fronts: (a) novel protein engineering tools, both experimental and computational, have significantly enhanced the toolbox for biocatalyst development. (b) The deactivation of biocatalysts under various stresses can be described quantitatively via rational models. There are several cases of spectacular leaps of stabilization after accumulating all stabilizing mutations found in earlier rounds. The concept that stabilization against one type of stress commonly also stabilizes against other types of stress is now experimentally considerably better founded than a few years ago.

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“…The racemic substrates were transformed to optically pure (>97% e.e.) (S)-berbine products with nearly complete conversion (98%) and up to 88% isolated yield (75).…”

Section: Pictet-spengler Cyclisation: Berberine Bridge Enzyme (Bbe)mentioning

confidence: 99%

Biocatalysis: A Status Report

Bommarius

2015

Annu. Rev. Chem. Biomol. Eng.

130

100

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“…[117] As a further extension of this methodology, this biocatalyst was combined with a reductant agent (morpholine·BH 3 complex) and the berberine bridge enzyme (BBE) to yield (S)-berbines. [118] BBE is a selective oxidase which catalyzes the intramolecular C-C coupling of (S)-reticuline leading to (S)-scoulerine. Only recently the substrate scope of BBE was studied, being suitable for the KR of these types of substrates.…”

Section: Scheme 17mentioning

confidence: 99%

Why Leave a Job Half Done? Recent Progress in Enzymatic Deracemizations

Díaz‐Rodríguez¹,

Lavandera

Gotor³

2015

CGC

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Abstract. In recent years the usefulness of enzymatic systems to obtain a single stereoisomerically pure compound starting from a racemate has been expanded. Moreover, current advances in protein engineering, molecular biology and modeling tools are the basis to improve the catalytic properties of enzymes to face novel synthetic challenges. Also, medium engineering and novel immobilization methods of (bio)catalysts are enhancing the productivity of biocatalytic processes making them suitable for being scalable. The development of multienzymatic protocols and the combination of enzymes with other catalysts are providing a wide range of synthetic possibilities that are expanding the scope of these transformations even at industrial scale. Herein we will describe an overview of recent (chemo)enzymatic deracemizations, focusing on the strategy employed (dynamic kinetic resolution, stereoinversion, cyclic deracemization or enantioconvergent process), the type of substrate (e.g., alcohols, amines, carboxylic acid derivatives or carbonylic compounds), and the biocatalyst(s) used.

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“…Recent work involved MAO‐N whole cells in bio‐chemo‐bio one‐pot transformation of rac ‐benzylisoquinolines to ( S )‐berbines. The ( R )‐selective MAO‐N D11 variant was cascade‐combined with two flavin‐dependent oxidases of opposite enantioselectivity, morpholine BH 3 and berberine bridge enzyme, to convert benzylisoquinoline in a one‐pot reaction . There are also new examples of one‐pot chemo‐biocatalytic cascades involving transaminase, MAO‐N and a non‐selective reducing agent for the synthesis of chiral 2,5‐disubstituted pyrrolidine building blocks, as well as for the deracemization and dealkylation of methylbenzylamine derivatives .…”

Section: Introductionmentioning

confidence: 99%

Chemo-biocatalytic one-pot two-step conversion of cyclic amine to lactam using whole cell monoamine oxidase

Zajkoska

Cárdenas-Fernández

Lye

et al. 2016

J. Chem. Technol. Biotechnol

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BACKGROUND Most biocatalysts currently involved in one‐pot chemoenzymatic cascades are pure enzymes, while whole cells and crude enzyme extracts remain unexplored. This work aims to develop a chemo‐biocatalytic one‐pot two‐step system involving whole cell monoamine oxidase (MAO, EC 1.4.3.4) coupled with a Cu‐based oxidative system (CuI/H2O2) for the transformation of 1,2,3,4‐tetrahydroisoquinoline (THIQ) to 3,4‐dihydroisoquinolin‐1(2H)‐one (DHIO). RESULTS MAO‐N variants D9 and D11 were tested as whole cell and crude lysate biocatalysts for biological oxidation. Whole Escherichia coli OverExpress C43(DE3) cells expressing MAO‐N D9 showed the best performance (Vmax = 36.58 mmol L−1 h−1, KM = 8.124 mmol L−1, maximum specific productivity 89.3 μmol min−1 g−1DCW) and were employed in combination with CuI/H2O2 in a sequential one‐pot two‐step process. The biotransformation was scaled‐up to the initial volume of 25 mL and after triple THIQ feeding, 48.2 mmol L−1 of the intermediate 3,4‐dihydroisoquinoline (DHIQ) was obtained with a yield of 71.3%. Afterwards, chemical catalysts (1 mol% CuI and 10 eq. H2O2) were added to the biologically produced DHIQ, which was transformed to ∼30 mmol L−1 DHIO at 69.4% overall yield. CONCLUSION As MAO‐N variants have wide substrate specificity, this work broadens the portfolio of one‐pot chemoenzymatic processes employing whole cell biocatalysts, representing an alternative to using pure enzymes. © 2016 Society of Chemical Industry

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Deracemization By Simultaneous Bio‐oxidative Kinetic Resolution and Stereoinversion

Cited by 73 publications

References 67 publications

Biocatalysis: A Status Report

Biocatalysis: A Status Report

Why Leave a Job Half Done? Recent Progress in Enzymatic Deracemizations

Chemo-biocatalytic one-pot two-step conversion of cyclic amine to lactam using whole cell monoamine oxidase

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