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Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE-2009-3-3-02 | Award Amount: 3.47M | Year: 2010

This project intends to engineer transaminase libraries that will be applied as the main enzymatic technology to deliver the amine functionality in the commercially valuable products of both chiral and bulk amine targets. These enzymes will be used in enzymatic cascades where simple starting materials are converted into the required intermediates for transamination or further enzymatic steps will be used to remove products from the transaminase reaction which will add value by extra functionality. This will also be supported by the development of enzymatic cascades to deliver efficient co-factor recycling and achieve the high conversions required for industrial use. A high throughput screening method based on a further enzymatic cascade will be developed. Engineering solutions will be used to overcome obstacles associated with the implementation of this core technology on a larger scale and integrate the use of other enzymes into the synthetic pathway to allow multi-step, multi-enzyme cascades to be used to deliver complex multi-functional amine products and processes. The industrial partner will target the development of enzymes from the project for specific application into their new products range. Life cycle analysis and environmental impact analysis will compare the final methods with conventional chemical synthesis and allow advantages to be objectively defined.

O'Reilly E.,University of Manchester | Iglesias C.,University of the Republic of Uruguay | Ghislieri D.,University of Manchester | Hopwood J.,University of Manchester | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2014

Biocatalytic approaches to the synthesis of optically pure chiral amines, starting from simple achiral building blocks, are highly desirable because such motifs are present in a wide variety of important natural products and pharmaceutical compounds. Herein, a novel one-pot ω-transaminase (TA)/monoamine oxidase (MAO-N) cascade process for the synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The reactions proceeded with excellent enantio- and diastereoselectivity (>94 % ee; >98 % de) and can be performed on a preparative scale. This methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the transaminase is not affected by the monoamine oxidase, and highlights the potential of this multienzyme cascade for the efficient synthesis of chiral building blocks. Mirror mirror on the wall: A ω-transaminase (ω-TA)/monoamine oxidase (MAO-N) cascade process for the asymmetric synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the TA reaction is not affected by the MAO-N catalyzed step. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Whiteker G.T.,Dow AgroSciences | Cobley C.J.,Chirotech Technology Ltd
Topics in Organometallic Chemistry | Year: 2012

This review summarizes the known commercial applications of rhodium-catalyzed olefin hydroformylation to fine chemical synthesis. Two manufacturing processes for Vitamin A utilize hydroformylation. Additional, recent examples of hydroformylation on multikilogram scale for synthesis of pharmaceutical building blocks have also been reported. Hydroformylation appears to be widely used in the fragrance industry, where aldehydes are ubiquitous. Numerous fragrance ingredients are commercially prepared by hydroformylation. There are no reports of agrochemical manufacturing processes which employ hydroformylation. In addition to commercial applications, examples of pharmaceutical, fragrance, and agrochemical products which have been prepared on small scale using hydroformylation are given. Hydroformylation appears to be well suited to fine chemical synthesis, and applications should increase as process chemists become more aware of its potential. © 2012 Springer-Verlag Berlin Heidelberg.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.63M | Year: 2016

The global need to move current human technologies into a sustainable future will have a great impact for the world of chemistry and related industries. In close concert with other disciplines, chemistry will be increasingly solicited to identify solutions that are practical, affordable and ultimately sustainable. To meet these objectives, not only research, but also chemical education will need profound reforms that have to be contextualized in the multidisciplinary and intersectoral picture of a sustainable development. It is propelled by these societal needs that, by educating and practising 14 ESRs, PHOTOTRAIN will ensure photo-triggered chemical process to play its central role in sustainability. By capitalising on the basic principles of supramolecular chemistry to program dynamic self-organized photoactive interfaces, it is intended to raise the creativity, knowledge, skills and capacity of the ESRs to conceive new ideas for reforming current industrial transformations into a new generation of light-triggered processes. The challenge of developing and transferring light-fuelled processes from a proof-of-principle to an exploitable process is to embark upon a dynamic configuration in which photoactive species are kept separated, act independently and are finally recycled. In particular, through the adoption of a microfluidic system in which programmed different phases allow the formation of photoactive interfaces, it is planned to implement photo-catalytic technologies at the industrial level for triggering stereoselective organocatalytic transformations (i.e., pharmaceutical applications) and/or solar fuels production. By the organisation of targeted individual projects and interdisciplinary secondements, ESRs will be guided toward attractive early-stage career opportunities as researchers, process chemists, chemical engineers and research managers in collective forms at various academic and research institutes, small and large enterprises, and NGOs.

Noonan G.M.,University of St. Andrews | Fuentes J.A.,University of St. Andrews | Cobley C.J.,Chirotech Technology Ltd. | Clarke M.L.,University of St. Andrews
Angewandte Chemie - International Edition | Year: 2012

Surprising selectivity: The first enantioselective hydroformylations of simple alkenes of type RCH 2CH=CH 2 to preferentially deliver the branched aldehyde product have been discovered using a new chiral ligand, named bobphos (see scheme). Established ligands are unselective in this reaction or show a slight preference towards the linear aldehyde. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crampton R.,University of Nottingham | Woodward S.,University of Nottingham | Fox M.,Chirotech Technology Ltd
Advanced Synthesis and Catalysis | Year: 2011

Bis-sulfamyl imines are shown to be potentially ideal substrates for rhodium-catalysed asymmetric additions of arylboron nucleophiles as they show: (i) near perfect enantioselectivities (11 examples, 98-99+% ee), (ii) good to excellent diastereoselectivities (10-32:1 rac:meso), and (iii) high functional group tolerance in removal of the low molecular weight protecting group via mild heating in aqueous pyridine. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 135.62K | Year: 2014

The purpose of the EDAM project is to test the feasibility of combining two well established technologies in order to develop an innovative process for the production and isolation of amino acids. Biocatalysis is a well established technology in the chemical and pharmaceutical industries, allowing the conversion of an amino acid precursor into a target amino acid using 1 or 2 enzymes. Electrodialysis membranes have been used for many years in the water purification industry, however wider applications of this technology remain under utilised. We propose to utilise a two enzyme reaction system to facilitate the production of amino acids. Subsequent application of a direct current electric field to the reaction mixture will then lead to electromigration of the charged amino acid species across an ion exchange membrane and product purification.

Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 494.54K | Year: 2013

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 308.28K | Year: 2016

The ImBioED project seeks to deliver improved economics for the production and isolation of amino acids without the need for extensive plant modifications. We intend to achieve this through the integration of biocatalysis and electrodialysis (ED) technologies. Biocatalytic processes are frequentlyimpeded by enzyme inhibition, which severely limits the scope for improving the volume efficiency of such processes. Building on promising results generated from a previous funded Innovate UK feasibility project we intend to utilise ED to remove inhibitory by-products from biotransformation processes, enabling us to achieve significantly improved levels of product accumulation.

Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 97.18K | Year: 2015

The purpose of this feasibility project is to create a deep systems biology level understanding of the stresses placed upon an organism, under a range of (fed-)batch and continuous fermentation conditions required for the large scale and high titre manufacture of biocatalysts, through the use of the complex analytical techniques of metabolomics and proteomics. The project seeks to understand how variation in the genetic constructs and process conditions used to direct protein production can affect the organism and how these effects might be mitigated against, minimised and controlled by further re-design of the genetic components, feed medium and process conditions. The development of robust fermentation processes has economic advantages, through both cycle time reduction and raw material efficiencies and will have clear impact beyond this feasibility study through the reliable and more economic commercial supply of enzymes to Industrial Biotechnology using industries.

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