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Application of Biocatalysis for the Synthesis of Chiral Amines

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Special Issue Information
Keywords
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A special issue of Catalysts (ISSN 2073-4344). This special issue belongs to the section "Biocatalysis".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 9045

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Special Issue Editors

Dr. Sarah L. Montgomery

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Guest Editor

Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Saffron Walden CB10 1RQ, UK
Interests: biocatalysis; synthetic biology; protein engineering; enzymatic cascades

Dr. Wojciech Zawodny

E-Mail Website
Guest Editor

Sosei Heptares, Cambridge, UK
Interests: biocatalysis; organic synthesis; late stage functionalization; drug discovery; medicinal chemistry

Special Issue Information

Dear Colleagues,

The last decade has seen spectacular growth in the range of biocatalysts available for the synthesis of chiral amines. Imine reductases now rival transition metal-based systems for catalytic imine reduction and reductive amination, while transaminases can catalyse the amination of carbonyl groups using a number of different amine donors. Wild-type and engineered amine dehydrogenases also catalyse reductive amination, with ammonia lyases enabling amination across some carbon-carbon double bonds. Amine oxidases can also be employed for the oxidative resolution of enantiomers.

Commercially available enzyme kits are expanding thanks to metagenomic discovery platforms and improved protein structure prediction, together with colorimetric or mass spectrometry-based activity screening. A combination of high-throughput characterisation and semirational mutagenesis has made protein engineering faster and more cost-effective than ever, which has important implications for the production of drug molecules, flavours and fragrances, and other high-value synthetic compounds.

This Special Issue aims to catalogue recent developments in biocatalysis for amine synthesis, particularly in cases where obtaining good enantiomeric excess at an α- or β-chiral centre is important for downstream applications. The goal of this Special Issue is to inform the reader about the state of the art in this area, the current opportunities and challenges, and perspectives on its future both in terms of chemical biology and applied organic synthesis.

Dr. Sarah L. Montgomery
Dr. Wojciech Zawodny
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

imine reductase
amine oxidase
transaminase
amine dehydrogenase
ammonia lyase
biocatalysis
reductive amination
metagenomics
directed evolution
high-throughput screening

Published Papers (3 papers)

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Research

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11 pages, 2308 KiB

Open AccessArticle

Novel Enzymatic Method for Imine Synthesis via the Oxidation of Primary Amines Using D-Amino Acid Oxidase from Porcine Kidney

by Nobuhiro Kawahara, Kunwadee Palasin and Yasuhisa Asano

Catalysts 2022, 12(5), 511; https://0-doi-org.brum.beds.ac.uk/10.3390/catal12050511 - 04 May 2022

Cited by 3 | Viewed by 2518

Abstract

During studies on the oxidative cyanation reaction catalyzed by a variant of D-amino acid oxidase from porcine kidney (pkDAO) (Y228L/R283G), an unexpected formation of 1-phenyl-N-(1-phenylethylidene)ethanamine (PPEA) was detected. The optimal reaction conditions for the synthesis of PPEA and the reaction mechanism were investigated using the pkDAO variant. The highest PPEA synthesis was obtained in the reaction with 150 mM (R)-MBA at pH 9.0 and at 20 °C. Since PPEA synthesis proceeded by trapping the intermediate 1-phenylethanimine (1-PEI) by ¹⁵N-labeled n-hexylamine, which is not a substrate for the pKDAO variant, it was deduced that PPEA would be synthesized by a nucleophilic substitution of 1-PEI by another molecule of (R)-MBA. PPEA was further identified by its conversion to bis(1-phenylethyl)amine (BPEA) through reduction with NaBH₄. Thus, a new enzymatic method of imine synthesis by oxidation of primary amine by the variant pkDAO was achieved for the first time. Full article

(This article belongs to the Special Issue Application of Biocatalysis for the Synthesis of Chiral Amines)

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17 pages, 3043 KiB

Open AccessArticle

Computational-Designed Enzyme for β-Tyrosine Production in Lignin Valorization

by Fei Peng, Habibu Aliyu, André Delavault, Ulrike Engel and Jens Rudat

Catalysts 2021, 11(11), 1310; https://0-doi-org.brum.beds.ac.uk/10.3390/catal11111310 - 29 Oct 2021

Cited by 3 | Viewed by 1751

Abstract

Lignin is an underutilized sustainable source of aromatic compounds. To valorize the low-value lignin monomers, we proposed an efficient strategy, involving enzymatic conversion from trans-p-hydroxycinnamic acids to generate valued-added canonical and non-canonical aromatic amino acids. Among them, β-amino acids are recognized as building blocks for bioactive natural products and pharmaceutical ingredients due to their attractive antitumor properties. Using computational enzyme design, the (R)-β-selective phenylalanine aminomutase from Taxus chinensis (TchPAM) was successfully mutated to accept β-tyrosine as the substrate, as well as to generate the (R)-β-tyrosine with excellent enantiopurity (ee > 99%) as the unique product from trans-p-hydroxycinnamic acid. Moreover, the kinetic parameters were determined for the reaction of four Y424 enzyme variants with the synthesis of different phenylalanine and tyrosine enantiomers. In the ammonia elimination reaction of (R)-β-tyrosine, the variants Y424N and Y424C displayed a two-fold increased catalytic efficiency of the wild type. In this work, a binding pocket in the active site, including Y424, K427, I431, and E455, was examined for its influence on the β-enantioselectivity of this enzyme family. Combining the upstream lignin depolymerization and downstream production, a sustainable value chain based on lignin is enabled. In summary, we report a β-tyrosine synthesis process from a monolignol component, offering a new way for lignin valorization by biocatalyst modification. Full article

(This article belongs to the Special Issue Application of Biocatalysis for the Synthesis of Chiral Amines)

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Review

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22 pages, 6026 KiB

Open AccessFeature PaperReview

Evolving New Chemistry: Biocatalysis for the Synthesis of Amine-Containing Pharmaceuticals

by Wojciech Zawodny and Sarah Louise Montgomery

Catalysts 2022, 12(6), 595; https://0-doi-org.brum.beds.ac.uk/10.3390/catal12060595 - 30 May 2022

Cited by 17 | Viewed by 3892

Abstract

Biocatalysis has become an attractive tool in modern synthetic chemistry both in academic and industrial settings, offering access to enantiopure molecules. In industry, biocatalysis found use in small molecule pharmaceutical development. For several amine-containing drugs, biotransformations were applied in the process routes, improving the original syntheses employing classical chemical methods. This review illustrates how and why biocatalysis has been applied to create safer, more efficient and less costly processes for the manufacture of chiral amine-containing pharmaceuticals and alkaloids. Several enzyme classes have been applied to syntheses of natural products, pharmaceutical products and their intermediates, including transaminases, imine reductases, monoamine oxidases and Pictet-Spenglerases. The routes with and without application of biocatalysis are compared, and the potential of these enzyme classes in redesigned synthetic routes to natural products, alkaloids and high-value chemicals is evaluated, using syntheses of sitagliptin, suvorexant, PF-04449913, MK-7246, vernakalant, GSK-2879552, boceprevir and (−)-strictosidine as examples. Application of biocatalysis in the synthesis of amine-containing pharmaceuticals constitutes a greener alternative to transition metal-catalysed routes, facilitates installation of chiral amine functionalities at a late stage of the synthesis and provides exquisite stereocontrol. Opportunities and challenges of biocatalysis for the synthesis of chiral amines are reviewed with respect to use in drug discovery and development. Full article

(This article belongs to the Special Issue Application of Biocatalysis for the Synthesis of Chiral Amines)

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