Deracemisation of benzylisoquinoline alkaloids employing monoamine oxidase variants

Schrittwieser, Joerg H.; Groenendaal, Bas; Willies, Simon C.; Ghislieri, Diego; Rowles, Ian; Resch, Verena; Sattler, Johann H.; Fischereder, Eva‐Maria; Grischek, Barbara; Lienhart, Wolf‐Dieter; Turner, Nicholas J.; Kroutil, Wolfgang

doi:10.1039/c4cy00642a

Cited by 26 publications

(23 citation statements)

References 62 publications

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“…In these cases reversal of enantioselectivity relative to the Turner results was not observed. 8 – 10 , 12b , 22 Relative to LG-I-D11, a higher ee-value (48%) was obtained for amine 6 by deracemization with mutant LG-J-B4. Interestingly, LG-J-B4 showed reversed stereoselectivity for amine 7 compared with LG-I-D11.…”

Section: Resultsmentioning

confidence: 95%

Simultaneous engineering of an enzyme's entrance tunnel and active site: the case of monoamine oxidase MAO-N

Yao

Gong

et al. 2017

Chem. Sci.

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Section: Resultsmentioning

confidence: 95%

Simultaneous engineering of an enzyme's entrance tunnel and active site: the case of monoamine oxidase MAO-N

Yao

Gong

et al. 2017

Chem. Sci.

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“…On the other hand, if high yields of racemic reticuline can be obtained from simple bacteria fermentation, a deracemization method for reticuline and similar benzoisoquinolines can be the next step. A method using stereoselective oxidation by a monoamine oxidase and reduction by ammonia-borane provided over 97% enantiomeric excess of (S)-reticuline [34].…”

Section: Biosynthetic Steps: Enzymes and Genesmentioning

confidence: 99%

Exploiting plant alkaloids

Schläger

Dräger

2016

Current Opinion in Biotechnology

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“…Then we applied the Turner‐deracemization technique to racemic valine ethyl ester and l ‐valine ethyl ester by using E. coli whole cells of CHAO and its double mutant Y321I/M226T in combination with a nonselective chemical reducing agent (NH 3 ⋅ BH 3 ) at pH 6.5 and 30 °C. The time–course study (Figure ) showed that the reactions of racemic valine ethyl ester and l ‐valine ethyl ester were fast and linear in the first 2 h and resulted in up to 99 and 77 % ee , respectively, for the mutant Y321I/M226T.…”

Section: Methodsmentioning

confidence: 65%

Accessing d‐Valine Synthesis by Improved Variants of Bacterial Cyclohexylamine Oxidase

et al. 2017

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Chemoenzymatic deracemization was applied to prepare dvaline from racemic valine ethyl ester or l-valine ethyl ester in high yield (up to 95 %) with excellent optical purity (> 99 % ee) by employing an ewly evolved cyclohexylamine oxidase (CHAO) variant Y321I/M226T exhibiting catalytic efficiency that was 30 times highert han that of the wildtype CHAO. Interestingly,C HAO and its variants showedo pposite enantioselectivity for valine ethyl ester and phenylalaninee thyl ester.d-Amino acids are important building blocks in pharmaceuticals, agrochemicals, and food additives. [1] d-Valine, in particular, exists widely in av ariety of agricultural pesticides, semisynthetic veterinary antibiotics, and pharmaceutical drugs, such as fluvalinate,v alnemulin, penicillamine, actinomycin D, fungisporin, and valinomycin. [2] It can also selectively inhibit the proliferation of fibroblasts in cell culture. [3] Therefore, the investigation of efficient methods for the synthesis of d-valine is of high importance. Thec urrent state-of-the-arta pproaches for the synthesis of d-valinei nclude chemical resolution, chemical asymmetric synthesis, and enzymatic transformation, each with its shortcomings. [2] Chemical resolution is commonly used in industry, [4] but it requires expensive chiral-resolving agents and complex experimentalp rocesses.C hiral auxiliaries, such as (R)and (S)-4-phenyl-2-oxazolidinone, in chemical asymmetric synthesis are expensive. [5] Unlike chemical methods, the enzymatic preparation of d-valine is an environmentally friendly process with high stereoselectivity and mild reaction conditions. To date, many enzymatic methods have been developed, for example,a symmetric degradation of d/l-valine by l-aminoa cid oxidase, [6] stereoselective hydrolysis by d-stereospecific amidohydrolase, [7] specific hydrolysis of d/l-5-isopropylhydantoin by

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Deracemisation of benzylisoquinoline alkaloids employing monoamine oxidase variants

Abstract: Deracemisation of benzylisoquinoline alkaloids was performed employing a recently developed variant of monoamine oxidase from Aspergillus niger (MAO-N variant D11).

Cited by 26 publications

References 62 publications

Simultaneous engineering of an enzyme's entrance tunnel and active site: the case of monoamine oxidase MAO-N

Simultaneous engineering of an enzyme's entrance tunnel and active site: the case of monoamine oxidase MAO-N

Exploiting plant alkaloids

Accessing d‐Valine Synthesis by Improved Variants of Bacterial Cyclohexylamine Oxidase

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