Quantitative Genetics of Hybrid Yeasts: overcoming sterility and biotechnological exploitation of diversity
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Biosciences
Abstract
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Technical Summary
Yeast hybrids are important in many industrial situations including various fermentations used to produce alcoholic beverages. These and other production strains have been improved upon over the decades by relying on mutations and selection. A much greater potential for improvement would be available if these strains were amenable to genetics and breeding. We will apply several mating/fusion techniques to create tetraploids out of existing hybrids and new hybrids created in the lab from extant species in the group. These will then be assessed for basic phenotypes and new genetically variable hybrids will be generated by putting the tetraploids through meiosis. Rather than being sterile the 4n hybrids will generate 2n diploid hybrids similar to the original sterile hybrid created but with new genetic combinations from the input parental strains of each species going into the hybrid. This will make the progeny amenable to the latest QTL analysis techniques in yeast using next generation sequencing on pools of selected individuals. The result will be first the generation of new hybrids with new characteristics, some will have improvements of desired traits. The analysis of these will provide the determination of why these new hybrids are improved. Finally some will be taken through fermentation processes with all the inherent stresses to determine whether the improved strains are still fit for fermentation purposes. Any useful strains will be protected by safe storage in the national culture collection (NCYC). Ultimately we will produce new hybrids to order for various fermentation and industrial purposes.
Planned Impact
Who will benefit from this research?
The opening up of hybrids to genetic analysis and breeding solves an age old problem and is of great potential benefit to several groups, primarily the fermentation industries producing alcoholic beverages but also to the biotech industries producing flavours and other high value compounds as well as those producing platform chemicals for new compound development, biofuels, bespoke compounds from engineered pathways, new enzymes, etc. Beyond the biotech and fermentation industries the methods could be beneficial to agriculture providing a means to bring in more genetic variation to hybrid crops that already have undergone tetraploidization. This research will also reach public and educational communities, such as agricultural and winery colleges (i.e. Plumpton College, East Sussex, UK), delivering awareness in new cutting-edge technologies, such as next generation sequencing and large-scale quantitative trait analysis, and specifically promoting UK basic science in the yeast physiology and evolution community.
How will they benefit from this research?
Immediate benefits will arise from the generation of new hybrid strains with improved properties, which will come along with the knowledge of the underlying genetics providing the improvement. Some beneficiaries will be able to utilize these immediately while other can use the approach on their production strains for improvement or can take the genetic knowledge to help engineer improvements in their strains.
What will be done to ensure that they have the opportunity to benefit from this research?
In addition to the traditional routes of publication and academic seminars, the results of this project will be communicated to target groups through the communications offices of the Universities of Leicester, Manchester and Nottingham and the BBSRC media office. Various activities of the PI, CoIs and Industrial Partner involve a wide range of industrial contacts including the Industrial Platform of the LACE programme under BSBEC, the Industrial members of the EU Cost Action Network on Bioflavours from Yeast, and attendance at conferences concentrating on applied aspects of yeast fermentation such as the ISSY in October 2014 and the Yeast in Bioeconomy in November 2013 where relevant outputs and methodologies will be disseminated. We will engage college students by publishing scientific articles in the "Biological Science Review" (http://www.bsr.manchester.ac.uk/) and by meeting them face-to-face in the 'Meet the Scientists' days, organized by Nowgen, a centre for genetics in healthcare, in Manchester.
Professional development for staff working on the project
The project will offer opportunities for the PDRAs to acquire additional skill sets. These will include training in quantitative trait analysis and NGS informatics as well as communication skills through scientific conferences and public engagement events. By attending the BBSRC Media courses, the PDRAs will achieve a better understanding on how to communicate science to the public and explain research strategies to policy makers and general communities.
The opening up of hybrids to genetic analysis and breeding solves an age old problem and is of great potential benefit to several groups, primarily the fermentation industries producing alcoholic beverages but also to the biotech industries producing flavours and other high value compounds as well as those producing platform chemicals for new compound development, biofuels, bespoke compounds from engineered pathways, new enzymes, etc. Beyond the biotech and fermentation industries the methods could be beneficial to agriculture providing a means to bring in more genetic variation to hybrid crops that already have undergone tetraploidization. This research will also reach public and educational communities, such as agricultural and winery colleges (i.e. Plumpton College, East Sussex, UK), delivering awareness in new cutting-edge technologies, such as next generation sequencing and large-scale quantitative trait analysis, and specifically promoting UK basic science in the yeast physiology and evolution community.
How will they benefit from this research?
Immediate benefits will arise from the generation of new hybrid strains with improved properties, which will come along with the knowledge of the underlying genetics providing the improvement. Some beneficiaries will be able to utilize these immediately while other can use the approach on their production strains for improvement or can take the genetic knowledge to help engineer improvements in their strains.
What will be done to ensure that they have the opportunity to benefit from this research?
In addition to the traditional routes of publication and academic seminars, the results of this project will be communicated to target groups through the communications offices of the Universities of Leicester, Manchester and Nottingham and the BBSRC media office. Various activities of the PI, CoIs and Industrial Partner involve a wide range of industrial contacts including the Industrial Platform of the LACE programme under BSBEC, the Industrial members of the EU Cost Action Network on Bioflavours from Yeast, and attendance at conferences concentrating on applied aspects of yeast fermentation such as the ISSY in October 2014 and the Yeast in Bioeconomy in November 2013 where relevant outputs and methodologies will be disseminated. We will engage college students by publishing scientific articles in the "Biological Science Review" (http://www.bsr.manchester.ac.uk/) and by meeting them face-to-face in the 'Meet the Scientists' days, organized by Nowgen, a centre for genetics in healthcare, in Manchester.
Professional development for staff working on the project
The project will offer opportunities for the PDRAs to acquire additional skill sets. These will include training in quantitative trait analysis and NGS informatics as well as communication skills through scientific conferences and public engagement events. By attending the BBSRC Media courses, the PDRAs will achieve a better understanding on how to communicate science to the public and explain research strategies to policy makers and general communities.
People |
ORCID iD |
Chris Powell (Principal Investigator) |
Description | The University of Nottinghams involvement in this collaboration started 12 months into the grant period (Autumn 2015). To date we have begun to develop a high throughput method for analysing key aspects of yeast physiology using phenotype microarray (PM). This technique can be applied to industrial samples and is currently being used to investigate the impact of substrate materials on fermentation potential. This is significance since it provides the vehicle to determine whether yeast strains are 'fit for purpose' which underpins the other aspects of this grant being conducted by our collaborators at Manchester and Leicester. During the project to date thousands of novel yeast hybrids have been produced. The characterisation tools described above have been expanded to form a 4-stage screening protocol for brewing strains. This is designed to investigate all aspects of yeast physiology which may impact on fermentation performance including: growth characteristics, stress tolerance, ethanol production, flocculation and response to inhibition (for example glucose repression of complex sugar asimilation). During the next stage of the project we will apply this screeing process to the developed strains with the goal of identifying viable production strains with enhanced properties. Subsequent investigations have allowed analysis of hybrids generated from within the sensu stricto yeasts, a group of organsims which includes parental strains for the vast majority of yeasts commonly used for industrial purposes. Initial screening was conducted on many thousands of yeast hybrids and at each stage preferential candidates were selected. This was largely based on viability and activity (growth) to remove the vast majority of isolates based on 'weak' physiological characteristics. The second round of screening included the first major analysis of traits useful for industrial fermentations. At this stage strains were screened for the capacity to assimilate and metabolise key sugars and to tolerate stress factors associated with industrial practices. The third screening stage was employed to look at more specific yeast attributes which can impact on fermentation characteristics. This primarily involved analysis of performance and function in laboratory scale fermentations. Key indicators included lag time, alcohol production, flavour generation and flocculation (cell binding capacity important for yeast collection and clairification of the product). The final round of screening was conducted on key isolates. This involved a more robust analysis at larger scale and comparison to targetted industrial and parental strains to determine 'fit for purpose' under a variety of industrial conditions. It also included analysis of functionaility on a variety of substrates to determine plasticity for industrial purposes. The data generated demonstrates proof that it is possible to generate intra- and inter-specific hybrids which display improvements ove the parental strains in key characteristics for brewing. This data is currently being prepared for pulication. |
Exploitation Route | The methodology developed allowed data to be generated that had a significant impact on our understanding of hybrid yeast phenotypes, not just for the brewing sector, but for all industrial processes which employ yeast. At the current time the industrial partner in this grant (now ABInBev since acquiring SABMiller in 2017) have expressed interest in adapting the methodology and tailoring the process to look for specific traits rather than to look at widespread diversity. ABInBev have an option to take this forward to produce production strains if this fits their current strategy. Data will also be published shortly, allowing other industries to implement similar strategies. Furthermore, data obtained from the present study has lead to further understanding of the imprtance of key cell parameters in phenotype inheritance. It is anticipated that this will form the basis of a subsequent grant application this year. |
Sectors | Agriculture Food and Drink Education Energy Environment Manufacturing including Industrial Biotechology |
Description | Preliminary data has been generated through the project with the purpose of characterising brewing yeast strains for phenotypic characteristics. A 4-stage screening process has been designed and presented at the major global brewing conference (World Brewing Convention, Denver, 2016). This has been adopted as a blueprint for screening yeasts by SABMiller Ltd. |
First Year Of Impact | 2016 |
Sector | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology |
Impact Types | Economic |
Description | BBSRC iCASE |
Amount | £99,668 (GBP) |
Funding ID | BB/M008770/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2017 |
End | 01/2021 |
Title | Phenotypic microarray for brewing yeast performance indicators |
Description | The method developed provides a tool for high-throughout screening of industrial yeast strains for desired characters. This can be tailored for different sectors, for example brewing, oenology and bioethanol production. The methodology used in the current study allows analysis of up to 5000 yeast hybrids at once for key performance indicators related to brewing. Specifically, this includes the ability to assimilate and metabolise major wort sugars rapidly and efficiently, and the capacity to tolerate stress factors associated with the process. |
Type Of Material | Biological samples |
Year Produced | 2016 |
Provided To Others? | No |
Impact | This development has allowed the identification and isolation of yeast strains which are likely to be used for industrial trials. |
Description | Yeast breeding collaborative |
Organisation | Anheuser-Busch InBev |
Country | Belgium |
Sector | Private |
PI Contribution | 1. Yeast screening. 2. Understanding the role of mitochondria in brewing yeast fermentation. 3. Providing expertise on traits desirable for brewing. |
Collaborator Contribution | Leicester:- Development of breeding strategies. Manchester:- Mitochondria inheritance. AB InBev :- Wort production and information on key performance indicators. |
Impact | Grant application in progress. |
Start Year | 2018 |
Description | Yeast breeding collaborative |
Organisation | University of Leicester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | 1. Yeast screening. 2. Understanding the role of mitochondria in brewing yeast fermentation. 3. Providing expertise on traits desirable for brewing. |
Collaborator Contribution | Leicester:- Development of breeding strategies. Manchester:- Mitochondria inheritance. AB InBev :- Wort production and information on key performance indicators. |
Impact | Grant application in progress. |
Start Year | 2018 |
Description | Yeast breeding collaborative |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | 1. Yeast screening. 2. Understanding the role of mitochondria in brewing yeast fermentation. 3. Providing expertise on traits desirable for brewing. |
Collaborator Contribution | Leicester:- Development of breeding strategies. Manchester:- Mitochondria inheritance. AB InBev :- Wort production and information on key performance indicators. |
Impact | Grant application in progress. |
Start Year | 2018 |