Deracemisation of benzylisoquinoline alkaloids employing monoamine oxidase variants

2014 ◽  
Vol 4 (10) ◽  
pp. 3657-3664 ◽  
Author(s):  
Joerg H. Schrittwieser ◽  
Bas Groenendaal ◽  
Simon C. Willies ◽  
Diego Ghislieri ◽  
Ian Rowles ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Monoamine Oxidase ◽  
Benzylisoquinoline Alkaloids

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

scholarly journals Dynamism and Cooperativity Essential for Efficient Catalysis in Aspergillus Niger Monoamine Oxidase

2019 ◽  
Author(s):  
Christian Curado-Carballada ◽  
Ferran Feixas ◽  
Sílvia Osuna
Keyword(s):  
Aspergillus Niger ◽  
Monoamine Oxidase ◽  
Active Site ◽  
Conformational Dynamics ◽  
Catalytic Efficiency ◽  
Building Blocks ◽  
Chiral Amine ◽  
Evolutionary Pathway ◽  
Accelerated Molecular Dynamics ◽  
Open States

<p><b> </b><i>Aspergillus niger </i>Monoamine Oxidase (MAO-N) is a homodimeric enzyme responsible for the oxidation of amines into the corresponding imine. Laboratory evolved variants of MAO-N in combination with a non-selective chemical reductant represents a powerful strategy for the deracemisation of chiral amine mixtures and, thus, is of interest for obtaining chiral amine building blocks. MAO-N presents a rich conformational dynamics with a flexible ß-hairpin region that can adopt closed, partially closed and open states. Despite the ß-hairpin conformational dynamics is altered along the laboratory evolutionary pathway of MAO-N, the connection between the ß-hairpin conformational dynamics and active site catalysis still remains unclear. In this work, we use accelerated molecular dynamics to elucidate the potential interplay between the ß-hairpin conformational dynamics and catalytic activity in MAO-N wild type and its evolved D5 variant. Our study reveals a delicate communication between both MAO-N subunits that impacts the active site architecture, and thus its catalytic efficiency. In both MAO-N WT and the laboratory evolved D5 variant, the ß-hairpin conformation in one of the monomers affects the productive binding of the substrate in the active site of the other subunit. However, both MAO-N WT and D5 variants show a quite different behaviour due to the distal mutations introduced experimentally with Directed Evolution. </p>

The Structure of Monoamine Oxidase from Aspergillus niger Provides a Molecular Context for Improvements in Activity Obtained by Directed Evolution

2008 ◽  
Vol 384 (5) ◽  
pp. 1218-1231 ◽  
Author(s):  
Kate E. Atkin ◽  
Renate Reiss ◽  
Valentin Koehler ◽  
Kevin R. Bailey ◽  
Sam Hart ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Monoamine Oxidase ◽  
Directed Evolution ◽  
Molecular Context

scholarly journals Hidden Conformations in Aspergillus niger Monoamine Oxidase are Key for Catalytic Efficiency

2019 ◽  
Vol 58 (10) ◽  
pp. 3097-3101 ◽  
Author(s):  
Christian Curado‐Carballada ◽  
Ferran Feixas ◽  
Javier Iglesias‐Fernández ◽  
Sílvia Osuna
Keyword(s):  
Aspergillus Niger ◽  
Monoamine Oxidase ◽  
Catalytic Efficiency

scholarly journals Dynamism and Cooperativity Essential for Efficient Catalysis in Aspergillus Niger Monoamine Oxidase

2019 ◽  
Author(s):  
Christian Curado-Carballada ◽  
Ferran Feixas ◽  
Sílvia Osuna
Keyword(s):  
Aspergillus Niger ◽  
Monoamine Oxidase ◽  
Active Site ◽  
Conformational Dynamics ◽  
Catalytic Efficiency ◽  
Building Blocks ◽  
Chiral Amine ◽  
Evolutionary Pathway ◽  
Accelerated Molecular Dynamics ◽  
Open States

<p><b> </b><i>Aspergillus niger </i>Monoamine Oxidase (MAO-N) is a homodimeric enzyme responsible for the oxidation of amines into the corresponding imine. Laboratory evolved variants of MAO-N in combination with a non-selective chemical reductant represents a powerful strategy for the deracemisation of chiral amine mixtures and, thus, is of interest for obtaining chiral amine building blocks. MAO-N presents a rich conformational dynamics with a flexible ß-hairpin region that can adopt closed, partially closed and open states. Despite the ß-hairpin conformational dynamics is altered along the laboratory evolutionary pathway of MAO-N, the connection between the ß-hairpin conformational dynamics and active site catalysis still remains unclear. In this work, we use accelerated molecular dynamics to elucidate the potential interplay between the ß-hairpin conformational dynamics and catalytic activity in MAO-N wild type and its evolved D5 variant. Our study reveals a delicate communication between both MAO-N subunits that impacts the active site architecture, and thus its catalytic efficiency. In both MAO-N WT and the laboratory evolved D5 variant, the ß-hairpin conformation in one of the monomers affects the productive binding of the substrate in the active site of the other subunit. However, both MAO-N WT and D5 variants show a quite different behaviour due to the distal mutations introduced experimentally with Directed Evolution. </p>

scholarly journals Hidden Conformations in Aspergillus niger Monoamine Oxidase are Key for Catalytic Efficiency

2019 ◽  
Vol 131 (10) ◽  
pp. 3129-3133
Author(s):  
Christian Curado‐Carballada ◽  
Ferran Feixas ◽  
Javier Iglesias‐Fernández ◽  
Sílvia Osuna
Keyword(s):  
Aspergillus Niger ◽  
Monoamine Oxidase ◽  
Catalytic Efficiency

Neuronal and Extraneuronal Uptake of 3H-Norepinephrine in the Heart of the Active Bat: An Electron Microscopic Radioautographic Study

1973 ◽  
Vol 31 ◽  
pp. 522-523
Author(s):  
Martin Hagopian ◽  
Michael D. Gershon ◽  
Eladio A. Nunez
Keyword(s):  
Smooth Muscle ◽  
Monoamine Oxidase ◽  
Vascular Smooth Muscle ◽  
Cardiac Muscle ◽  
Maximum Rate ◽  
External Medium ◽  
Extraneuronal Uptake ◽  
Electron Microscopic ◽  
Cardiac Tissues ◽  
High Affinity

The ability of cardiac tissues to take up norepinephrine from an external medium is well known. Two mechanisms, called Uptake and Uptake respectively by Iversen have been differentiated. Uptake is a high affinity system associated with adrenergic neuronal elements. Uptake is a low affinity system, with a higher maximum rate than that of Uptake. Uptake has been associated with extraneuronal tissues such as cardiac muscle, fibroblasts or vascular smooth muscle. At low perfusion concentrations of norepinephrine most of the amine taken up by Uptake is metabolized. In order to study the localization of sites of norepinephrine storage following its uptake in the active bat heart, tritiated norepinephrine (2.5 mCi; 0.064 mg) was given intravenously to 2 bats. Monoamine oxidase had been inhibited with pheniprazine (10 mg/kg) one hour previously to decrease metabolism of norepinephrine.

Inhibition of Rat Brain Monoamine Oxidase Activities by Psoralen and Isopsoralen: Implications for the Treatment of Affective Disorders

2001 ◽  
Vol 88 (2) ◽  
pp. 75-80 ◽  
Author(s):  
Ling Dong Kong ◽  
Ren Xiang Tan ◽  
Anthony Yiu Ho Woo ◽  
Christopher Hon Ki Cheng2Note
Keyword(s):  
Monoamine Oxidase ◽  
Rat Brain ◽  
Affective Disorders ◽  
Brain Monoamine
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