![Page 1: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/1.jpg)
Dr Andrew EllisTechnical Director
The Latest Tools and Technologies for Enzyme Discovery and Development
![Page 2: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/2.jpg)
Genomics & Metagenomics
Enzyme Bioinformatics
Protein Engineering
EnzymeDiscovery and Development
![Page 3: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/3.jpg)
Enzyme Discovery: Bioinformatics
![Page 4: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/4.jpg)
Enzyme Discovery: Metagenomics
![Page 5: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/5.jpg)
Protein Engineering: Methods?
Technique Advantages Disadvantages
Directed
Evolution
- Structural knowledge not required - More effective with high throughput screening
- Requires specialist screening techniques
- Experimentally demanding
- Creates many inactive sequences
Ancestral
Reconstruction
- All sequences are functional - Unfocussed in terms of characteristics
- Results rarely industrially applicable
- Computationally demanding
Semi-Rational
Design
- Smaller, focussed libraries - Requires structural knowledge
- More effective with high throughput screening
Rational
Design
- Few variants per round
- Allows more in-depth screening
- Requires robust structural knowledge
Computational
Screening
- Dramatic reduction in variants per
round
- Requires robust structural knowledge
- Computationally demanding
De novo
Design
- Allows access to new function /
chemistry
- Requires robust structural knowledge
- Computationally demanding
- Depends on diversity of input structures
UAA
Incorperation
- Improvements over conventional
methods
- Low throughput with current technology
![Page 6: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/6.jpg)
Protein Engineering: Providers
Service Provision Cost Time-scale IP Engineering Examples
Arzheda Final enzyme $1,000,000 1 year (on
average)
With client thermostability, increased activity,
novel activity, substrate scope
Dezblyme Mutation
guidance
Final enzyme
€3,500 /
protein / day
1 - 2 days plus With client stability, thermostability, solubility,
temperature optimum
Dngtd2 Final enzyme $100,000 -
1,000,000
3 months - 3
years
With client substrate scope, increased activity,
solubility, stereoselectivity
PKJEACCEL Mutation
guidance
€100,000 -
300,000
2 weeks - 6
months
Shared enantioselectivity, ligand and / or
protein interactions, thermostability
Evofdxcatal Final enzyme On enquiry - Shared -
Moulomics Final enzyme £100-10,000 Days to weeks With client ligand interaction, thermostability
Ingenhyza Own enzymes - Several months - -
Sesam Final Enzyme €50,000-
100,000
6-12 months With client -
Bioprodict Database to
guide design
€5,000-15,000 2-4 weeks With client -
clecta Own enzymes - 6-12 months - -
Codtfex Final enzymes $200,000 -
$800,000
9-12 months - thermostability, increased activity,
novel activity, substrate scope
![Page 7: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/7.jpg)
Genomics & Metagenomics
Enzyme Bioinformatics
Protein Engineering
EnzymeDiscovery and Development
![Page 8: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/8.jpg)
Enzyme Discovery: Sequencing
• >100,000,000 million enzymes.
• Since NGS, generation of DNA sequence data is increasing exponentially. The data is outstripping our capacity to analyse it.
• DNA sequence data generated in 1 week of sequencing will take 2 to 4 weeks to assemble and analyse or screen. Constantly playing catch-up!
![Page 9: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/9.jpg)
MinION
Tim
e
1 h
1 d
1 w
PacBio
Time to answer
A. Costessi - BaseClear
![Page 10: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/10.jpg)
Enzyme Discovery: Gene synthesis
96 Oligos = 1 Gene
Traditional MethodsBased on 96-well plate
Twist Bioscience1st Silicon-based Synthesis Platform
> 1 Million Oligos = 9,600 Genes
![Page 11: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/11.jpg)
Strains
Fermentation Optimisation
EnzymeManufacture
Downstream processing
![Page 12: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/12.jpg)
Future
1st Industrial RevolutionSteam, mechanism
2nd Industrial RevolutionElectricity, chemicals, mass production
3rd Industrial RevolutionComputers, electronics
4th Industrial RevolutionNBIC convergence
The 5th
Industrial Revolution
Scientific method Open society
Technological Change
+120 years
+80 years
+50 years
+30 years
1760…
1960…
2010…
2040…1880…
Credit for slide to David W. Wood (twitter: @dw2)
![Page 13: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/13.jpg)
20 Tech Breakthrough Areas by 2025
Wearable computers, Augmented Reality,
remote virtual avatars
Nanomaterials with super-strength
& resilience
GeoengineeringE.g. massive carbon
removal
Cryptocurrencies:Decentralised
consensus systems
Big Data and the Internet of Things: many fewer secrets
Brain scanning: consciousness &
creativity decoded
Mind enhancing drugs (or hardware
stimulation, e.g. tDCS)
3D fabrication, with Atomically Precise
Manufacturing
Synthetic biology: reprogramming DNA,
new life forms
Rejuvenation biotech: Stem cell therapies,
synthetic organs
Driverless cars, drones: much safer, greener
transport
Synthetic meat: abolition of animal
suffering
Ubiquitous green energy: major
reduction of oil usage
Automated robot workers: nurses,
soldiers…
Cognitive computing in healthcare: Most
doctors redeployed
Rational management or decisions and
resources
Virtual companions more compelling than
real ones
Credible cryonics: mass market suspensions
Quantum computing: Moore’s Law
-> Rose’s Law
Sanitation & nutrition: Clean water, cities,
vaccinations…
http://anticipating2025.com/book/ Credit for slide to David W. Wood (twitter: @dw2)
![Page 14: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/14.jpg)
Future perspective: Development
2005
2017
2020
6 12 18 24 30 36
Time (months)
€100K - €200K
€500K - €1M
< €100K
![Page 15: The Latest Tools and Technologies for Enzyme Discovery and](https://reader031.vdocument.in/reader031/viewer/2022013018/61d0d4a01d76ef669b66417f/html5/thumbnails/15.jpg)
www.biocatalysts.com ¦ [email protected] ¦ [email protected]