the latest tools and technologies for enzyme discovery and
TRANSCRIPT
Dr Andrew EllisTechnical Director
The Latest Tools and Technologies for Enzyme Discovery and Development
Genomics & Metagenomics
Enzyme Bioinformatics
Protein Engineering
EnzymeDiscovery and Development
Enzyme Discovery: Bioinformatics
Enzyme Discovery: Metagenomics
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
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
Genomics & Metagenomics
Enzyme Bioinformatics
Protein Engineering
EnzymeDiscovery and Development
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!
MinION
Tim
e
1 h
1 d
1 w
PacBio
Time to answer
A. Costessi - BaseClear
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
Strains
Fermentation Optimisation
EnzymeManufacture
Downstream processing
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)
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)
Future perspective: Development
2005
2017
2020
6 12 18 24 30 36
Time (months)
€100K - €200K
€500K - €1M
< €100K
www.biocatalysts.com ¦ [email protected] ¦ [email protected]