Download Increased Crop Yield Through Improved Photosynthesis

Increased Crop Yield Through
Improved Photosynthesis
4th International Conference on Agriculture and Horticulture
Beijing, July 14, 2015
Andy Renz, Vice President Business Development
100% Increase in Productivity Required by 2050
Required yield increases are significantly
higher than historical yield increases.
Ray et al, 2013, PLoS ONE
2nd Generation Ag Biotech – Abiotic Stress Tolerance & Yield Increase
2025
2nd generation traits
1st generation traits
Yield traits represent the largest opportunity in ag biotech
2nd Generation Ag Biotech – Abiotic Stress Tolerance & Yield Increase
• Excellent results and products from molecular breeding
– AQUAmax™ corn from Pioneer
– Artesian™ corn from Syngenta
– Droght tolerant rice from IRRI
• Opportunity and Challenge for GM approaches:
– Monsanto/BASF: largest partnership in the history of Ag Biotech
R&D: $2.5 billion(!)
• HTP screens in model and crop plats
• Field testing in crops (commercial germplasm)
• First prducts: Droughtgard™ corn launched in 2013 (CspB)
– Benson Hill Biosystems:
• Focus on yield improvement through improved photosynthesis
Can Improvement in Photosynthesis Increase Crop Yields?
Long et al. (2006) Plant Cell Envir 29
Yield Potential:
•
•
•
•
•
Y = 0.487 * St * ɛi * ɛp* ɛc
0.487: percentage of photosynthetically active radiation
St : total incident solar radiation across the growing season
Ɛi: : light interception efficiency, i.e. ability of canopy to capture sunlight
Ɛp : partitioning efficiency, i.e. harvest index
Ɛc : conversion efficiency, i.e. combined gross photosynthesis of the
canopy, less all plant respiratory losses
Quite optimi
through breed
Far bel
threshold lim
Recent Publications Confirming this Hypothesis (1)
Simkin et al (2015) J Exp Bot 66:40
Recent Publications Confirming this Hypothesis (2)
Ambavaram et al (2014) Nature Communications 5:530
Photosynthesis is the Most Promising Target to Increase Crop Productivity
I.
II.
III.
IV.
Enhance photosynthetic efficiency
Increase overall energy availability
Increase photosynthetic productivity in a canopy
Maintain photosynthesis during abiotic stresses
Focus on rate-limiting
steps of primary
metabolism
Carbon
shuttle
Sugars
“fine tuning” to provide
genetic variability that
otherwise would never occur
Benson-Calvin
cycle
Starch
production
ATP + NADPH
Energy
Light
Harvesting
Requires use of multi-genic approaches and precisely controlled gene expression
Benson Hill Biosystems – Company Summary
• The Photosynthesis Company TM
• Focus: Increased Crop Yield through Improved Photosynthesis
• Discovery: Integrated, systems-based approach to engineering plant primary
metabolism
• One platform – multiple product opportunities:
corn, sugarcane, soybean, rice, wheat, cotton, oil palm, canola, Eucalyptus,…
• GM- and non-GM product concepts
• World-class plant growth and genomics facility licensed and in use
• Pre-Series A company; more partnership revenues than venture capital
• Partnerships with global leaders
Benson Hill Biosystems – Integrated Platform with Focus on Photosynthesis
Field testing
in crops
State of the art
phenotyping
Aerial
imaging
Genomic selection &
Computational breeding
Crop
models
Gene-based Modifications
Transgenic &
Non-GM
Genome
editing
Deep knowledge about
photosynthesis
Gene regulatory
networks
PSKbase TM – Unique omics
and computational platform
Network plasticity
analysis
Synthetic Chemistry
Crop performance &
Crop protection
Biologicals
Stimulants &
microbes
Partnership with Donald Danforth Plant Science Center
• IP/license access to labs of Tom Brutnell and Todd Mockler
– 35+ FTEs working on photosynthesis, computational and systems biology, transcriptional
regulatory networks, novel targets and promoters, etc.
• Enablement of CapEx Lite with access to:
Tissue Culture and Transformation Facility (2,000ft2)
Potting area with soils handling room (1,900ft2)
33 Conviron chambers and 18 Conviron rooms (3,000ft2)
36 Greenhouses (44,000ft2)
Bioinformatics Core: 800+ processors, 3 TB memory, and a
single, high-performance 204 TB storage area network
– Other Cores: Proteomics, Mass Spectrometry, Integrated Microscopy, X-Ray Crystallography
– High-throughput robotics assay platforms
– High-throughput plant phenotyping system
–
–
–
–
–
Iterative Lead Identification and Optimization
___
Lead________
Transcriptomics
Association mapping
Genomic selection
Physiology
Modeling
PSKbase™
Optimization__
Expression profile
Protein modification
Localization
PSKbase™ is BHB’s central vehicl
integrating and interpreting data,
tool for rapid cu
prioritization,
selection of prom
trait candida
Mode of Action__
Reverse genetics
Over-expression
Cell biology
Setaria viridis as mod
for C4 crops,
rice and Brachypodiu
for C3 crops
Pipeline Summary
PSKbase™: Various datasets
(proprietary and publicly available)
Trait
Candidates
Proprietary algorithm-based
approaches
to integrate datasets
Genes
Target identification
(PSKbase™ prioritization)
>800
321
140
38
12
Lead prioritization:
validation assays and
in planta validation
Crop plant
validation
Yield field
trials
Licensed Genes
Discovery: PSKbaseTM and Computational Biology Platform
PSKbase™: Various datasets
(proprietary and publicly available)
Trait
Candidates
Proprietary algorithm-based
approaches
to integrate datasets
Genes
Target identification
(PSKbase™ prioritization)
>800
321
140
38
12
Lead prioritization:
validation assays and
in planta validation
Crop plant
validation
Yield field
trials
Licensed Genes
Example 1: C4 Bundle-Sheath and Mesophyll Cell Photosynthesis Gene Networks
Leaf development
Section A
Section C
Section B
Setaria
Illumina RNA-seq, 3 reps for each cell population
Mesophyll
Bundle sheath
Example 2: Wheat Leaf CO2-responsive Gene Expression Atlas
Low [CO2]
Ambient
[CO2]
High [CO2]
[CO2] – responsive functional gene candidates
baseline
developmental
and metabolic
gene expression
Example 2: Photosynthesis Target Identification from Gene Networks
Samples from Wheat
Photosynthetic Subnetwork
Automated Proprietary
Analytics Pipeline
336 genes
and
93 TFs
Gene Network
Example 2: Network Plasticity Analysis Identifies Candidate Genes
89 wheat loci that had significant plastic gene network interactions with core
photosynthesis genes
Gene X
Gene Y
Gene Z
Gene A
Gene B
[CO2]
Our approach identifies both specific candidates and their regulatory partners
that are responsive to atmospheric conditions.
Environmental Conditions and Photosynthesis are Linked
• Example project: used for cross-referencing with photosynthesis network
analyses: 4,128 genes – cold, salt, drought, and heat-responsive
• Stress-associated regulons identify
co-expressed genes implicated in
abiotic stress responses
and primary metabolism
Brown – Drought
Black – Salt
Red – Heat
Blue – Cold
Purple and Green – multiple interactions
In planta Validation of Leads
PSKbase™: Various datasets
(proprietary and publicly available)
Trait
Candidates
Proprietary algorithm-based
approaches
to integrate datasets
Genes
Target identification
(PSKbase™ prioritization)
>800
321
140
38
12
Lead prioritization:
validation assays and
in planta validation
Crop plant
validation
Yield field
trials
Licensed Genes
C4-Specific Transcription Factors identified by PSKbase™
Project Objectives: Demonstrate improvements in photosynthesis, plant growth, and yield
by overexpression of photosynthesis-associated transcription factors identified through
developmental transcriptomics and bioinformatic analyses.
Background/Rationale:
• Benson Hill Biosystem’s PSKbase™ is a
proprietary tools used for identifying
and prioritizing trait candidates.
• Using PSKbase™, 8 uncharacterized
maize transcription factors were
identified for testing in a C3 system –
Brachypodium distachyon.
• To provide for diversity of expression
profiles, 4 promoters were selected
and combined with each of the 8 TFs,
for a total of 32 constructs.
C4-Specific Transcription Factors: High Hit Rate in Model Plants
In T1 Brachypodium plants, 5 of the 8 selected Transcription factors have phenotypes with significant increases in bio
In each graphic: left plants are wild-type (non-transgenic)
Brachypodium distachyon, and right plants are T1 Brachypodium
distachyon plants containing BHB candidate
BH15 Enhances Carbon Availability in C3 and C4 Plants
• Significantly improved photosynthetic efficiency, WUE, and yield in soybean, tobacco, and
Arabidopsis
• Soybean greenhouse and field yield
increases of >15% and >7%, respectively
• Optimizing by:
– Co-expressing with genes encoding
rate-limiting steps of photosynthesis
– Employing spatial- and temporalspecific expression profile
• Advancing into maize and rice
• First constructs in maize being tested
in hybrids in 2015 field season
Multi-year soybean data
BH30 Increases Water Availability and Photosynthesis
• Over-expression of BH30 results in increased hydraulic
conductivity and plant growth in Arabidopsis and poplar,
particularly under heat conditions
• Quantification of vessel size shows ~33% increase in vessel
mean diameter
BH33 is a Well Characterized Sink Strength Lead
• Naturally-occurring, well characterized enzyme in maize grain, mutated for improved
thermal stability and enzyme kinetics
• Previous mutated versions have shown promise in field trials of multiple crops
• Iterative mutation has resulted in BH33, which has improved characteristics relative to
enzymes previously expressed in plants
• Maize field testing in 2014 showed up to 24% increase in ear weight relative to control
(null segregants with otherwise identical genetic background)
• Inbred data in greenhouse also show positive results
• Hybrid seed production completed and field trials in 2015 season ongoing
• Coupling with numerous other source-focused trait candidates
• Testing initiated in multiple other crops
BH71: Increased Seed Yield and Nitrogen Utilization for C4 Crops
• Significant increase of biomass and seed yield, in particular under N-limiting conditions;
• Strong Lead for sugarcane, corn and sorghum;
Dry Weight
1.40
Total Seed Weight
1000.0
1.20
800.0
>130%
increase
0.80
WT
0.60
Null Segregant
Homozygote
0.40
Total Seed Weight (mg)
Dry Weight (g)
1.00
600.0
>400%
increase
W
N
400.0
H
200.0
0.20
0.00
0.0
Low N
High N
Low N
High N
Improving Photosynthesis is Broadly Applicable & Enables Many Product Opportu
Product Opportunities
Computational and
systems-biology
Setaria (C4),
Brachypodium & rice (C3)
model plant platforms
CORN
SORGHUM
SOYBEANS
ENERGY GRASSES
COTTON
POPLAR
CANOLA
PLATFORM
Genetic “toolbox” for
manipulating primary
metabolism
Photosynthesis
know-how and focus
EUCALYPTUS
OTHER TREES
POTATO
TOMATO
SUGARCANE
YAMS
WHEAT
SWEET POTATOES
RICE
SUGAR BEET
ALFALFA
CASSAVA
OIL PALM
TOBACCO
MILLET
OTHER VEGETABLES
ALGAE
Path to Commercialization – “Go to Partner”
• Seed market is consolidated,
with high barriers to entry
REQUIRES
PARTNERSHIPS
– Elite germplasm, i.e. plant genetics
• Biotech trait discovery and development is entry point for participating in the
most valuable and high-growth segment
• To monetize traits, seed are used as value capture mechanism
– Premium pricing for seed containing biotech trait(s)
– Value sharing via royalties, which can be pre-calculated (flat rate) or based on percentage
trait value retained by seed company
• Benson Hill Biosystems is partnering on a crop-by-crop basis
– Non-exclusive deal structures in corn and soybean
– Exclusive and alternative deal structures in other crops
Thank You
Non-GM Product Concept: Genome Editing Technology
Prerequisite: most BHB lead genes are derived from crops
Validate targets identified through PSKbase™
Platform agnostic: CRISPR/Cas, TALEN, Meganucleases
Precise introduction of foreign genes
Modification of target gene expression
Replacement of genes by improved versions
Uniform expression levels (only few events required)
Modification of native genes through small insertions
– Regulatory motifs to modify gene expression
– Specific base pair changes to modify activity/specificity of native enzymes
• Potential Non-GMO approach
– Of particular relevance for wheat, rice, etc.
• USDA confirms BHB’s approach as non-regulated, i.e. non-GM products
•
•
•
•
•
•
•
•