Frank Sargent
f.sargent@dundee.ac.uk
At the CECHR Symposium 2016 Molecular Microbiology School of Life Sciences, University of Dundee, Scotland
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Frank Sargent Molecular Microbiology School of Life Sciences, University of Dundee Co-Chair BBSRC Committee B – Plants, Microbes, Food and Sustainability Transforming lives
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The Bioeconomy landscape Health products & tools Food
Wood, Paper, Fibres, etc.
Synthetic Biology & Industrial Biotechnology
The bioeconomy has policy relevance to many government Departments, for example: BIS interest
DH interest
Defra interest
DECC interest
DfT interest
Why is industrial biotechnology and bioenergy important? SUSTAINABILITY (DECC/DfT/DEFRA) • • • •
Maintaining citizens’ lifestyles in an era of increasing cost of ‘fossil’ hydrocarbon based energy and feedstock chemicals. 80% reduction in greenhouse gas emissions by 2050. 27% of energy from renewable sources by 2030. End the use of fossil fuels by 2099? (CoP 21)
VALUE TO THE UK ECONOMY •
Estimated at £8B by 2025. (see: Biotech Britain 2015)
HEALTH •
(BIS)
(BIS Strategy for Life Sciences 2013/DoH)
Source of valuable products for improving healthcare (e.g. antibiotics, pharmaceutical intermediates, biopharmaceuticals).
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Biofuels: (bio)hydrogen as a fuel
IBB and BBSRC
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Bioenergy ď Ž
What types of biofuels are there?
Bio-mass Bio-hydrogen
Bio-ethanol Bio-methanol
Bio-butanol Bio-diesel
Bio-methane Transforming lives
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2H2 + O2 → 2H2O Best energy-to-weight ratio of any fuel Wide range of flammability (4-75 %) Low ignition energy
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also: very low density so difficult to store
1937: New Jersey Transforming lives
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2H2 + O2 → 2H2O Best energy-to-weight ratio of any fuel Wide range of flammability (4-75 %) Low ignition energy Versatile: can also be used in fuel cells
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Efficient conversion to electricity
Fuel cell ~60% Engine ~30%
H2 + ½O2 H2O -286 kJ/mol
Anode
Cathode
Proton/Polymer Electrolyte Membrane (PEM) Fuel Cell Transforming lives
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99% of H2 in current use made by steam reformation of fossil fuel
Stream
methane reforming
CH4 + H2O CO + 3H2 The
water-gas shift reaction
CO + H2O CO2 + H2 Transforming lives
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Bio-H2 production
1. ‘Dark’ Fermentation enteric bacteria (E. coli), Clostridia, extremophiles
2. Photobiological Hydrogen Production
purple bacteria, Cyanobacteria, green algae
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acetate glucose succinate
ethanol
H2 !!
lactate formate A formate dehydrogenase plus a hydrogenase make the formate hydrogenlyase (FHL) complex
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formate
formate
periplasmic side
cytoplasmic side
PDB code 3Q7K: L端 et al. (2011) Science 332: 352-354 Transforming lives
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formate
formate
periplasmic side
cytoplasmic side
PDB code 3Q7K: L端 et al. (2011) Science 332: 352-354 Transforming lives
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formate
periplasmic side
HycD
HycC
cytoplasmic side
formate
‘Hyd-3’
= Ni-Fe cofactor = Fe-S cluster = molybdenum cofactor
PDB code 1FDO: Boyington et al. (1997) Science 275: 1305-1308
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size exclusion chromatography
MW
metal content (by ICP-MS) 0.1 Mo: 1 Ni: 25 Fe
FHL HycD
HycC
443 200
FdhF, HycB,E,F,G (210,547 Da)
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HycB,E,F,G (131,174 Da) FdhF only (79,373 Da)
66 BN-PAGE
McDowall et al. (2014) PNAS 111:E3948-56; McDowall et al.(2015) FEBS Letters 589, 3141-3147.
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H2 production in vitro driven by formate
formate (HCO2-) ď‚Ž CO2 + H2 H2-sensing electrode
gas chromatography
Sodium formate solution (pH 6.5) was added to 50 mM (final concentration) and the reaction was allowed to proceed at 25ËšC. McDowall et al. (2014) PNAS 111:E3948-56 and Conny Pinske (unpublished) Transforming lives
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EARTH
Nitrogen 0.1-30% Hydrogen CO2
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Nitrogen 0.1-30% Hydrogen CO2
‘forward’
‘reverse’ periplasmic side HycD
HycD
HycC
HycC
cytoplasmic side
H+??
CO2 fixation to formate before the evolution of glycolysis? Nitschke & Russell (2012) J. Mol. Evol. 69: 481–496.
Transforming lives
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‘forward’
‘reverse’ periplasmic side
HycD
HycD
HycC
HycC
cytoplasmic side
H+??
CO2 fixation to formate before the evolution of glycolysis? Nitschke & Russell (2012) J. Mol. Evol. 69: 481–496.
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HycD
HycC
• hya hyb (no other hydrogenases) • fdhE (no other formate dehydrogenases) • pflA (no way to metabolise formate)
time (min)
Incubate with CO2 and H2 then detect formate production by HPLC Transforming lives
Conny Pinske www.dundee.ac.uk
HycD
HycC
CO2 + H2 ď‚Ž formate (HCO2-)
Incubate with CO2/H2
Detect formate production by HPLC Transforming lives
Conny Pinske www.dundee.ac.uk
ď‚ž
To optimise CO2 conversion using engineered bacteria (Sasol, St Andrews) ď‚ž
To explore conversion of formate to other C1 compounds (Ingenza, Edinburgh)
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Transforming lives
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Biofuels: (bio)hydrogen as a fuel
IBB and BBSRC
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Public Engagement
IB Catalyst Research Council Funding
BIVs & Proof of Concept Funds Administered by Network
Network Leadership Network Director Network Manager Management Board
Commercialisation
Innovate UK Funding
International Funding
Scale up and Demonstration
Policy Engagement
ÂŁ18M funding for 13 networks www.bbsrc.ac.uk/bbsrcnibb
IB Catalyst 5 year funding programme BBSRC, EPSRC, Innovate UK ÂŁ45M funding for 2014-15
Seeking funding jointly with Innovate UK and EPSRC
VISION UK bioscience research delivering new products & processes key to the bioeconomy and driving economic growth for the UK and worldwide
BBSRC NIBB (2014-2019) Biorefining
Bioprocessing
Biocatalysis
Novel Chassis
HVC/Natural Products
Cross Cutting
www.bbsrc.ac.uk/bbsrcnib | nibb@bbsrc.ac.uk
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Encouraging new ideas and academicbusiness interactions (Oct. 2015) Proof of Concept grants • 77 PoC projects awarded, Network spend of ~ £3.1M (total~ £11.4M) • Industry has invested at least £394k (majority in-kind contributions) in 48 PoC projects
Business Interaction Vouchers • 85 BIVs have been awarded after 18 months, Network spend ~ £423k • Industry has invested ~ £469k (majority in-kind contributions) 30
Industrial Biotechnology Catalyst Rounds 1-3: Jan 2014-July 2015 (Round 4 concludes March 2016)
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IB Catalyst: Scientific Scope and Challenges •
Translation of research on biological processes into industrial processes.
•
Projects can be academic- or industry-led with collaborating partners.
Challenges • • • • •
•
Production of fine and speciality chemicals and natural products Production of commodity, platform and intermediate chemicals and materials (e.g. plastics, resins, textiles). Production of liquid and gaseous biofuels. Production of (glyco) peptides and proteins (e.g. antibiotics, recombinant biologics). Novel or improved upstream or downstream processes to reduce costs or improve efficiency. To consider the economic, environmental and social impacts of the research.
Industrial Biotechnology Catalyst
IB Catalyst: Headline figures •
235 projects have applied to the IB Catalyst requesting a total of £309 million.
• A total of 66 projects have been funded relating to £58.8 million in grants. • Across the 66 funded projects £11.9 million has been leveraged from industrial partners: 20% leverage.
Industrial Biotechnology Catalyst
Is there any evidence for BBSRC NIBB activities and success under the IB Catalyst? IB Carb: two successful proposals in R2 Translation on chemoenzymatic transformations in glycoscience. HVCfP: R2 Industrial Research on Industrial saponins (company-led) LBNet/BioCatNet: R2: Feasibility of the manufacture of bio-based polyester from cellulose (company-led) CBM Net: R3 Translation on engineering resistance to toxic products. Metals in Biology: R3 Translation on Enzyme catalysed chemical synthesis using hydrogen gas (initially a BIV). BIOCatNet: R3 Translation: Biocatalysts for active pharmaceutical ingredients.
Industrial Biotechnology Catalyst
Future funding opportunities Spending review-dependent managed activities: • IB Catalyst Round 5 (scheduled to open Spring 2016). • EC Co-Fund Biotechnology (Combined IB/SynBio/SystemsBio ERANetlike mechanism). Global Challenge Research Fund (GCRF) • Announced in the Comprehensive Spending Review: £1.5Bn fund to support UK research of relevance to developing countries. • Alignment with UK Gov. Official Development Assistance objectives which has promotion of economic development and welfare as the key aims. • BBSRC has identified immediate contributions such as agriculture/food security/ diet and health as its initial areas. • Broader activities in biotechnology including use of wastes and residues and supporting technologies (eg big data) will also have impacts. 35
Key Past Members Dr Magali Roger - BBSRC-funded postdoc
Dr Marta Albareda Contreras - H2020 Marie Skłodowska-Curie Fellow Mr Ciaran Lamont - BBSRC-funded PhD student Ms Marília de Assis Alcoforado Costa - CAPES-funded PhD student Mr Richard Owen - MRC-funded PhD student Ms Lucia Licandro Lado - Dundee-funded PhD student Mr Alex Finney - BBSRC-funded PhD student
Dr Jen McDowall (Bath)
Dr Lisa Bowman (Imperial) Dr Ciarán Kelly (Imperial) Dr Conny Pinske (Halle)
Collaborators Prof Fraser Armstrong (Oxford) Prof Gary Sawers (Halle) Prof Bill Hunter (Dundee) Prof Tracy Palmer (Dundee) Dr Alison Parkin (York)
Thanks to‌‌.. Dr Colin Miles Head of Strategy, Industrial Biotechnology and Bioenergy colin.miles@bbsrc.ac.uk
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