Biochemical production of succinic acid from biorefinery glycerol: De-risking, scale-up, and sustainability
Lead Research Organisation:
University of Manchester
Department Name: Chem Eng and Analytical Science
Abstract
This project addresses the bioproduction of succinic acid, a top-added value chemical, through the fermentation of crude glycerol, which is the main byproduct of biodiesel production. Currently, succinic acid is predominantly manufactured from petrochemicals or by the fermentation of glucose/sugars. The bioconversion of crude glycerol will not only valourise this fully renewable side-stream which is essentially a biorefinery waste, hence significantly improving the biorefinery economy, but can also provide a sustainable production route with reduced carbon footprint and a favourable economic potential. Hence, the aim of this project is to holistically assess the feasibility of the route from the crude glycerol to the final succinic acid product. A combination of experimental methodologies at a range of scales, from the bench- to the pilot-scale, computational tools, including economic models and process simulators, and market analysis will be employed in order to: (i) prove the feasibility of the downstream process, (ii) benchmark the final succinic acid product against the chemical market standards, (iii) successfully optimise the scale up of the fermentation process to 750 litre bioreactors (iv) identify and engage commercial end users. These objectives should constitute a significant step in reducing the risk of the proposed bioprocess in order to attract industrial investments, hence moving closer towards its industrial uptake and application.
Technical Summary
This project is concerned with the bioproduction of Succinic Acid, a top added-value chemical from crude biorefinery glycerol, through batch fermentation, using an appropriately adapted strain of Actinobacillus Succinogenes. It involves a creative synergy between the academic process developers, industrial process implementation specialists as well as industrial process adopters. The aim of the project is to quantitatively assess the feasibility of this process in terms of the quality of the final product, compared to the market standards and of the efficiency of the fermentation at the pilot scale. In parallel market analysis will seek to engage end-users to the next stage of industrial research. A combination of experimental methods, covering a range of different scales from the bench- to the pilot scale, and computational tools will be employed for this purpose. In particular, the project aims to: experimentally verify the downstream process for the production of the final product, benchmark the final succinic acid against market standards, prove the feasibility of the fermentation scale-up in 750 L bioreactors, and computationally assess the economic and environmental feasibility of the overall process.
There is a number of innovative aspects involved, which have been filed in recent patent applications, including (i) the generation of an appropriately adapted strain with improved ability to convert glycerol to succinic acid (ii) an optimised fermentation methodology for SA production (iii) the development of validated predictive computational models of the bioprocess and (iv) the construction of integrated biorefinery simulators coupled with economic models of the process. There is also extensive know-how that is associated with the design and optimisation of the process.
There is a number of innovative aspects involved, which have been filed in recent patent applications, including (i) the generation of an appropriately adapted strain with improved ability to convert glycerol to succinic acid (ii) an optimised fermentation methodology for SA production (iii) the development of validated predictive computational models of the bioprocess and (iv) the construction of integrated biorefinery simulators coupled with economic models of the process. There is also extensive know-how that is associated with the design and optimisation of the process.
Planned Impact
As described in proposal submitted to TSB
Publications
Rigaki A
(2020)
Double substrate limitation model for the bio-based production of succinic acid from glycerol
in Biochemical Engineering Journal
| Description | Developed a novel technology for the bioconversion of crude biorefinery glycerol to succinic acid, which is a top added-value chemical. The technology includes the scale-up of the process, the downstream separation of the final product as well as a techno-economic evaluation of the overall plat design to ensure the commercial feasibility of the process. In addition continuous two production bioreactor designs have been invented: one involving cell recycle and the other cell immobilisation. Our idea comprises a number of innovations, which have been filed in recent patent applications: - Generation of a strain of A. succinogenes with improved ability to convert glycerol to SA. - An optimised fermentation methodology, producing SA from crude glycerol with high yield and high final concentrations as well as low co-product formation. - Validated predictive computational models of the bioprocess including the bioconversion of both substrates involved (crude glycerol and CO2) for process optimisation and design purposes. - An optimised continuous fermentation methodology using recycling of cells, resulting in high yields and improved productivities. - Validated predictive computational model for the continuous bio production of Succinic acid using cells recycle. - An optimised continuous fermentation technology using cell immobilisation, resulting in significantly improved productivities and reduced downstream processing requirements. - A validated model continuous fermentation technology using cell immobilisation - A holistic computational model of the integrated biorefinery co-producing biodiesel and succinic acid to assess the economic and environmental feasibility. This also allows us to efficiently design the downstream process and to assess potential alternative options. - Extensive know-how that is associated with the design and optimisation of the process |
| Exploitation Route | The aim is to create a licensable fully-scaleable technology that converts crude glycerol to succinic acid. In this respect the technology will be able to be adopted by companies for biosuccinic acid production. Furthermore, the results form this work can be used by other researchers in the area of industrial biotechnology, metabolic engineering and (bio)process design to construct relevant processes and to analyse, model and optimise important biotechnological process features. Results form this work can also be used for complete plant design including techno-economic analysis and environmental impact in order to construct environmentally-friendly bio-based manufacturing processes. Also results can be used to decipher the complex metabolism underlying such biobased processes. The separations community can use this work to design efficient downstream separation extraction processes. In addition he have developed and recently published an new model of the succinic acid fermentation process which takes into account both carbon substrates, glycerol and carbon dioxide and can be successfully used to design and optimise the fermentation process. |
| Sectors | Chemicals,Energy,Environment,Manufacturing, including Industrial Biotechology |
| URL | http://www.uk-cpi.com/news/cpi-university-manchester-work-improve-economic-proposition-uk-biodiesel-manufacture/ |
| Description | Research from the work is being supported by the chemical industry and results are in the short term being used to create a licensable technology for the supporting company to adopt for production purposes. In addition the research consortium is seeking additional funding through InnovateUK and Royal society opportunities for the next step of development bringing the technology one step closer to market application. It is important to recognise that we have developed a sustainable route to succinic acid which also presents a sustainable route to a 1,4 butanediol which is an intermediate for plastics, solvents, chemicals and fibres. Evidence from a study of end-users of succinic acid conducted by PHS Consulting suggests that there is market need for a sustainable source of BioSA providing the price is right. One respondent identified a competing source of BioSA as being too costly for the specification on offer. The feedback from the market was that the biosuccinic acid that companies were aware of was technical grade - that is to say that it was suitable for use in manufacturing chemicals but not ideal for food or pharmaceutical use. Respondents saw an unsatisfied requirement for biosuccinic acid manufactured according to Good Manufacturing Practice - GMP. This is an approach to manufacturing that provides for systematic quality assurance and traceability and labelling systems to ensure that products are suitable for human consumption. Research findings are currently being used in a new PhD that started November 2018, which is focusing on the continuous bio production of succinct acid. We are currently developing a continuous fermentation process using the findings from this work in conjunction with a new double substrate model we have developed in order to significantly improve the process in terms of productivity and production rates. In addition we are working on a new techno-economic analysis of the overall process, from biomass to final product, taking into account our new improved process developments. |
| First Year Of Impact | 2015 |
| Sector | Chemicals,Manufacturing, including Industrial Biotechology |
| Impact Types | Economic |
| Title | Adapted Microorganism |
| Description | Adapted microorganism for optimal production of succininc acid from crude glycerol |
| Type Of Material | Cell line |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| Impact | Working on the developer of a licensable technology based on this method |
| Title | Process model |
| Description | Computational model for the bioproduction of succinic acid. In addition a new double substrate fermentation model has been recently published. |
| Type Of Material | Model of mechanisms or symptoms - in vitro |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | Tool used in the scale-up of the bioprocess. New model being used to develop a significantly improved continuous fermentation process, optimised with respect to productivity and production rate. |
| Title | A model of continuous bio production of Succinic Acid |
| Description | An experimental-based computational model of a continuous bioreactor with cell recycle for the bioproduction of Succinic Acid from glycerol. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | The model allows for the efficient selection of optimal operating conditions including feed flow rates and recycle ratio for the bio production of Succinic Acid, achieving high yield and significantly improving productivity compared to the batch case. |
| Title | A model of continuous bio production of Succinic Acid using cell immobilisation |
| Description | A detailed distributed parameter computer model describing the bio production of Succinic Acid using cell immobilisation in a packed-bed arrangement. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | The model allows for the optimisation of the bioreactor design and of the selection of operation/environmental conditions, leading to significant increase in productivity and to savings in downstream processing. |
| Title | Process model |
| Description | Double substrate process model for the bioproduction of succinic acid though actinobacillus succinogenes |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Speed-up of batch process scale-up and design. Also speed-up of development of continuous bioreactors for Succinic Acid production. |
| Description | UoM-CPI |
| Organisation | Centre for Process Innovation (CPI) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | My research team worked on the fermentation process to produce succinic acid from biorefinery glycerol. We also worked on the full transfer of the technology to the Centre of Process Innovation (CPI) so that (i) we could prove transferability of the technology. (ii) CPI could contribute on the scale-up as well as on the downstream processing and hence construct an integrated technology. My team also worked on the modelling and the techno-economic evaluation of the complete flowsheet in order to identify the most valuable processing options. We also worked on optimising the fermentation conditions and the batch-to-batch scale up conditions. We also conducted studies on the strain robustness. |
| Collaborator Contribution | CPI worked on the scale-up of the process and on the transferability of the fermentation. They also confirmed the strain ability to assimilate different grades of crude glycerol. They also performed analysis on different samples of industrial crude biorefinery glycerol. They also experimentally investigated a number of downstream processing options to achieve (i) a high purity solid succinic acid product (ii) a liquid phase di-butyl succinate product in line with the specifications of our other industrial partner (Chemoxy -see next entry). CPI also worked with us and with Chemoxy to evaluate the process and contributed to the economic data used to populate the flowsheet constructed by UoM. |
| Impact | The outcomes that have resulted from this partnership are: (i) A viable bioprocess from crude glycerol to dibutyl succinate with a fermentation scale of 20L. Quality of results actually confirms the viability of fermentation at higher scales. (ii) A CPI newsletter outlining the aims of the project as well as the main outcomes expected: http://www.uk-cpi.com/news/cpi-university-manchester-work-improve-economic-proposition-uk-biodiesel-manufacture/ (iii) A "next-sage" funding application to InnovateUK in order to bring the technology a step closer to commercialisation. This is an interdisciplinary collaboration involving: Chemical and Bioprocess engineering Industrial Biotechnology Biology Microbiology |
| Start Year | 2015 |
| Description | UoM-Chemoxy |
| Organisation | Centre for Process Innovation (CPI) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Technical contributions. Background of the idea. Initial economic assessment of the process viability. Experimental and computational design of novel process. |
| Collaborator Contribution | Technical contributions, techno-economic assessment of the viability of the process. Contributing to design of process sale-up as well as to the design of the downstream process |
| Impact | Patents on the process are being filed. Licensable technology for industrial application is being designed. Only 6 moths from start of the project have passed, so publications are being prepared but not yet submitted. |
| Start Year | 2015 |
| Description | UoM-Chemoxy |
| Organisation | Chemoxy International |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Technical contributions. Background of the idea. Initial economic assessment of the process viability. Experimental and computational design of novel process. |
| Collaborator Contribution | Technical contributions, techno-economic assessment of the viability of the process. Contributing to design of process sale-up as well as to the design of the downstream process |
| Impact | Patents on the process are being filed. Licensable technology for industrial application is being designed. Only 6 moths from start of the project have passed, so publications are being prepared but not yet submitted. |
| Start Year | 2015 |
| Title | SELECTION OF IMPROVED MICROBIAL STRAINS FOR PRODUCTION OF SUCCINIC ACID FROM GLYCEROL |
| Description | Provided are methods for generating a microorganism with improved ability to convert glycerol to succinic acid. These methods comprise combining a microorganism with ability to convert glycerol to succinic acid and a medium containing glycerol to produce a fermentation mixture; allowing fermentation to occur such that succinic acid is produced; and assaying for an indication of glycerol metabolism. These latter two steps may be repeated as necessary. Also provided are microorganisms generated in this manner, particularly bacteria deposited at the NCIMB on 13 th April 2011 with the Accession Number NCIMB 41825. A method of producing succinic acid from glycerol is also provided, this method comprising: mixing a microorganism according to claim of the invention with a medium comprising glycerol to produce a fermentation mixture; and incubating the fermentation mixture, under conditions that promote fermentation to produce succinic acid, until succinic acid is produced. Succinic acid produced by such methods is also provided. |
| IP Reference | WO2012143736 |
| Protection | Patent granted |
| Year Protection Granted | 2012 |
| Licensed | Commercial In Confidence |
| Impact | Sustained collaborations with industry and CPI catapult centre. Establishment of a viable and economically providable biosuccinic acid route |
| Description | CPI Newsletter |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Newsletter from Centre of Process Innovation describing the collaboration: "CPI and University of Manchester work to improve the economic proposition for UK biodiesel manufacture" |
| Year(s) Of Engagement Activity | 2015,2016 |
| URL | http://www.uk-cpi.com/news/cpi-university-manchester-work-improve-economic-proposition-uk-biodiesel-... |
| Description | ECCE2015 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Presentation at 10th European Congress of Chemical Engineering |
| Year(s) Of Engagement Activity | 2015 |
| Description | Outreach public talk targeting high school graduates UG students and MSc students in Hanoi Vietnam |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Outreach public talk targeting high school graduates UG students and MSc students in Hanoi Vietnam. The target of the talk was to instigate interest in studies in the UK and in particular in the field of Biotechnology. This was under the umbrella of a British Council STEM tour in Vietnam, |
| Year(s) Of Engagement Activity | 2016 |
| Description | Outreach public talk targeting high school graduates UG students and MSc students in Ho Chi Minh City Vietnam |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Public talk at Ho Chi Minh City under the umbrella of the British Council STEM tour. Around 50-60 people attended involving parents, high school students, UG students and MSc students interested in UK university education. the talk sparked a large number of questions on UK studies and in the field of Biotechnology in particular and was followed by 1 to 1 meetings with interested parts. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Yamaguchi Young Scientist Seminar |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Keynote lecture on biotechnological approached and tools, at 11th Young Scientist Seminar, Yamaguchi Japan. Audience included postgraduate, undergraduate students and professional practitioners from a large number of Asian countries, including Japan, Thailand, Malaysia, Vietnam, Laos, Indonesia. The lecture sparked vivid questions and discussion afterwards and many members of the audience have followed up, showing vivid interest in the area. |
| Year(s) Of Engagement Activity | 2015 |