About This Project
Plants capture CO2 from air to build sugars, which allows them to grow through a process called photosynthesis. While nature has slowly refined photosynthesis over 3.2 billion years, the key enzyme (a molecular machine) responsible for capturing CO2 is slow and makes mistakes. Here, we develop new methods to improve the CO2 capture efficiency and selectivity, which will lay the foundation for plant-based climate correction strategies.
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What is the context of this research?
Our planet is under treat by anthropogenic CO2 release, which must be captured to reverse climate change. While photosynthesis is been responsible for >90% of global CO2 capture , the key enzyme catalyzing this capture – called RuBisCO – is too slow to keep up with our increased CO2 output .
Given the need for sustainable approaches for climate correction, RuBisCO is considered to be one of the most important targets for protein bioengineering [3,4]. However, traditional bioengineering strategies have failed to improve RuBisCO's activity .
Why? Researchers have some ideas: some posit that this reflects biochemical tradeoffs in RuBisCO catalysis , but new data suggests that the issue may be connected to RuBisCO’s inability to adapt quickly through natural evolution .
What is the significance of this project?
Protein evolution is constrained by function and expression in nature , resulting in only 1-100 mutations every 10,000,000 years . However, laboratory directed evolution can proceed at 1-5 mutations per week to improve bioactivity .
While RuBisCO has been subjected to directed evolution , traditional strategies can be slow and laborious to carry out, resulting in only modest gains to date. Further, these evolutionary methods have a high false-positive discovery rate and rely on existing genes or canonical amino acids found in nature.
New strategies are needed. Developing solutions to these issues would catalyze a paradigm shift in methods to improve RuBisCO-catalyzed CO2 capture, laying the foundation for sustainable climate correction using photosynthesis.
What are the goals of the project?
Starting in Nov 2023, we will develop an innovative strategy to evolve RuBisCOs with improved activities while simultaneously addressing all prior issues.
Our approach will integrate autonomous and continuous directed evolution that allows RuBisCO to explore hundreds of mutations every minute, a roughly 100-fold improvement as compared to traditional approaches. Our strategy will overcome false-positive bottlenecks, and be compatible with novel genes or amino acids to uncover new-to-nature enzymes altogether.
We will apply these state-of-the-art resources to improve RuBisCO CO2 capture kinetics by up to 300% (state-of-the-art to date = 60%). Findings from our work will lead to engineered plants with optimized RuBisCOs to capture CO2 with improved efficiency.
We are requesting funding from Homeworld Collective to complete our potentially game-changing work in optimizing nature's leading strategy for CO2 capture. Specifically, our work will focus on engineering and evolving the key photosynthetic enzyme RuBisCO towards a greater CO2 capture rate. The proposed "go-no go" series of experiments will lay the foundation for CO2-driven protein bioengineering strategies by our lab and many others. Looking forward, our success here will catalyze translational efforts in plants, algae, and even microbes using our engineered enzymes for CO2 capture.
Our findings will catalyze a paradigm shift in RuBisCO bioengineering approaches within a short time compared to prior approaches. Based on our experience, we will be able to complete the proposed experiments within 12 months. We have a strong track record over ~15 years in biosensor development, enzyme continuous evolution, and biochemical validation. Detailed milestones are on the right.
Feb 15, 2024
Development of a high-throughput evolution strategy that applies phage-assisted continuous evolution (PACE) to RuBisCO
Apr 15, 2024
Submit a 6-month progress report
May 15, 2024
Genome mining RuBisCO homologs, applying ancestral enzyme reconstruction methods to RuBisCO, and subjecting all variants to bioactivity analyses
Jul 15, 2024
Completion of RuBisCO continuous evolution campaigns using modern, ancestral, or stabilized homologs in PACE
Aug 15, 2024
In vitro biochemical analysis of evolved RuBisCO variants, and (potentially) carrying out supplementary PACE campaigns to further improve CO2 capture
Meet the Team
We are a young, diverse, and highly motivated lab at the bleeding edge of synthetic biology and protein bioengineering. For over 15 years, I have developed a strong track record as a trainee and independent investigator in affecting problems of global importance across diverse fields, including agriculture, medicine, and materials research. In this work, my lab will develop a streamlined and biologically-inspired solution to combat climate change.
Over eons, nature has adapted to changes in environments all over our planet. This process (called evolution) is the mechanism by which biological molecules such as DNA, RNA and proteins acquire changes, leading to organisms that are best adapted to their environments. All of life as we know it derives from this mechanism, but evolution has taken billions of years to innovate and create the diversity of molecules we see all around us.
Compared to the time that Nature has had to refine biological systems, humanity has affected monumental changes to the environment in what seems like the blink of an eye. These changes are among the most pressing problems of our time, including climate change, antibiotics resistance, plastics accumulation, and many others. Nature simply cannot adapt quickly enough to ameliorate these issues.
In an effort to solve these crises, research in the Badran Lab expedites the process of Darwinian evolution to allow biological systems to innovate much faster than nature does. We apply these rapid evolutionary technologies to create new DNA, RNA and proteins that have new functions never before seen in nature, which in turn allows us to develop unique strategies to solve these looking global issues. Broadly, our research aims to fundamentally address current or future natural disasters using sustainable, biologically-driven strategies. Our work also focuses on biomedical, materials, and environmental elements that we believe are essential for humanity’s continued prosperity.
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