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 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>

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 Ultra-high throughput functional enrichment of large monoamine oxidase (MAO-N) libraries by fluorescence activated cell sorting

The Analyst ◽  
2018 ◽  
Vol 143 (19) ◽  
pp. 4747-4755 ◽  
Author(s):  
Joanna C. Sadler ◽  
Andrew Currin ◽  
Douglas B. Kell
Keyword(s):  
Monoamine Oxidase ◽  
Directed Evolution ◽  
High Throughput ◽  
Cell Sorting ◽  
Oxidase Activity ◽  
Functional Enrichment ◽  
High Throughput Screen ◽  
Fluorescence Activated Cell Sorting ◽  
E Coli

A novel ultra-high throughput screen forin vivodetection of oxidase activity inE. colicells and its application to directed evolution.

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

Directed Evolution of the Enzyme Monoamine Oxidase (MAO-N): Highly Efficient Chemo-enzymatic Deracemisation of the Alkaloid (±)-Crispine A

ChemCatChem ◽  
2012 ◽  
Vol 4 (9) ◽  
pp. 1259-1261 ◽  
Author(s):  
Ian Rowles ◽  
Kirk J. Malone ◽  
Laura L. Etchells ◽  
Simon C. Willies ◽  
Nicholas J. Turner
Keyword(s):  
Monoamine Oxidase ◽  
Directed Evolution ◽  
Highly Efficient ◽  
Enzyme Monoamine Oxidase

scholarly journals Recent progress in directed evolution of stereoselective monoamine oxidases

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiaqi Duan ◽  
Beibei Li ◽  
Youcai Qin ◽  
Yijie Dong ◽  
Jie Ren ◽  
...  
Keyword(s):  
Amino Acid ◽  
Monoamine Oxidase ◽  
Directed Evolution ◽  
Recent Progress ◽  
Acid Oxidase ◽  
Tertiary Amines ◽  
Amino Acid Oxidase ◽  
Monoamine Oxidases ◽  
The Subject ◽  
Low Activity

Abstract Monoamine oxidases (MAOs) use molecular dioxygen as oxidant to catalyze the oxidation of amines to imines. This type of enzyme can be employed for the synthesis of primary, secondary, and tertiary amines by an appropriate deracemization protocol. Consequently, MAOs are an attractive class of enzymes in biocatalysis. However, they also have limitations in enzyme-catalyzed processes due to the often-observed narrow substrate scope, low activity, or poor/wrong stereoselectivity. Therefore, directed evolution was introduced to eliminate these obstacles, which is the subject of this review. The main focus is on recent efforts concerning the directed evolution of four MAOs: monoamine oxidase (MAO-N), cyclohexylamine oxidase (CHAO), D-amino acid oxidase (pkDAO), and 6-hydroxy-D-nicotine oxidase (6-HDNO).

Semi-rational Directed Evolution of Monoamine Oxidase for Kinetic Resolution of rac-Mexiletine

2015 ◽  
Vol 176 (8) ◽  
pp. 2267-2278 ◽  
Author(s):  
Zhenming Chen ◽  
Yuanhui Ma ◽  
Mengyan He ◽  
Hongyang Ren ◽  
Shuo Zhou ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Directed Evolution ◽  
Kinetic Resolution

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>

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