Harnessing Synthetic Biology to Tackle Evolutionary Shortcomings
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Synthetic Biology, commonly referred to as SynBio, represents one of the most rapidly advancing fields in science today, where existing biological systems are reengineered for novel applications. This broad arena encompasses innovative solutions such as bacteria for biofuel production, microbes for environmental cleanup, and genetically modified rice that synthesizes beta-carotene—a precursor to Vitamin A typically found in carrots.
According to Jane Calvert, a professor at the University of Edinburgh specializing in Science and Technology Studies, Synthetic Biology embodies the concept of applying engineering principles to biological systems. This approach aims to:
- Comprehend biological mechanisms through the lens of available technologies.
- Utilize these technologies to analyze, design, and reconfigure biological components, ultimately enhancing quality of life.
As the field progresses, it shifts from traditional scientific endeavors that seek to describe nature, instead focusing on the potential applications of biology. Massimiliano Simons, a philosopher of Science and Technology at the University of Ghent, aptly summarizes this shift:
> Rather than detailing existing biological systems, the aim is to explore biological potentials.
The COVID-19 pandemic has significantly heightened interest in this domain, with the World Economic Forum identifying SynBio as a crucial technology for addressing inefficiencies and unsustainable practices. The market for Synthetic Biology is projected to expand, fueled by increased investments and a growing demand for innovative solutions in healthcare, pharmaceuticals, and environmental sustainability.
The possibilities appear limitless if we can manipulate and enhance biological processes as we do with technology. Successfully creating new biological processes based on existing frameworks could optimize these processes further as our understanding and technological capabilities advance. This raises an intriguing question: can Synthetic Biology resolve evolutionary inefficiencies that have persisted over time?
Evolutionary Inefficiencies and Constraints
The implications of evolutionary theory often spark debate. A nuanced understanding of the complexities involved reveals that nature has not always optimized biological processes. Contrary to the popular idea of "survival of the fittest," which suggests continuous improvement in organisms, evolution does not invariably lead to optimal outcomes. Two primary factors contribute to this phenomenon:
- Selection can only act on the genetic variations present. For instance, a cheetah cannot evolve to become faster if no faster gene variant exists.
- Biological systems must work with existing materials, as they cannot create something from nothing—hence, mythical creatures like winged horses remain fiction.
As a result, we often observe biological features or processes that persist despite being less efficient than expected, rather than being eliminated by natural selection. While this discussion does not delve into the origins of these inefficiencies, an example can illustrate the concept.
Example of an Inefficient Enzyme — RuBisCO
RuBisCO is an enzyme believed to be the most abundant protein on Earth, playing a vital role in carbon fixation—the conversion of carbon dioxide (CO?) into a usable form of carbon for organisms, such as glucose. It governs the Calvin-Benson-Bassham cycle, which is estimated to account for approximately 90% of global carbon fixation. However, as noted by researchers Tobias J. Erb and Jan Zarzycki from the Max Planck Institute, RuBisCO is notably inefficient for several reasons:
- It exhibits a slow turnover rate, taking longer to convert starting materials into products, which limits its carbon-fixing capacity. This inefficiency arises partly because it must differentiate between CO? and oxygen (O?) during reactions. While specificity is crucial for enzymes, it often comes at the expense of speed. Notably, for every five CO? molecules processed, RuBisCO also reacts with two O? molecules.
- The reaction with O? produces a harmful compound called glycolate-2-phosphate (2PG), which is toxic to plant cells and inhibits other enzymes. To eliminate this toxic byproduct, plants undergo photorespiration, consuming oxygen and releasing carbon dioxide, which ultimately reduces CO? levels. This energy-intensive process detracts from the plant's growth potential, representing a significant constraint.
In this article, "constraint" refers to a limitation preventing optimal performance. An evolutionary constraint arises from pressures experienced during the evolutionary process. In RuBisCO's case, speed was sacrificed for accuracy, adapting to the pre-oxygen atmosphere. As oxygen levels rose, the enzyme required a mechanism to prevent excessive reactions with O?—demonstrating how evolutionary history can constrain current biological functions.
Despite its historical viability, the rapid growth of the human population throughout the 20th century—fueled by technological advancements—necessitates a doubling of crop yields by 2050 to meet increasing demand. With other essential components for carbon fixation, like water and light, typically abundant, the efficiency of carbon fixation itself becomes a major limiting factor in agricultural productivity. This scenario underscores the urgent need for innovations in agriculture that support a burgeoning human population while being environmentally sustainable. Enhancing carbon fixation processes could address this challenge.
This brings us back to the earlier question: how can synthetic biology address the inefficiencies identified in biological systems?
Synthetic Designs to Overcome Natural Constraints
While the scope of Synthetic Biology may not extend to macro-level alterations, research indicates that at the micro and molecular levels, engineering can enhance existing systems and mitigate constraints. Here are two examples: one in agriculture and the other in medicine.
1. A Synthetic Pathway for Enhanced Carbon Dioxide Fixation In Vitro
Researchers have developed a new 17-enzyme system that improves carbon fixation by approximately 30%, circumventing evolutionary and environmental constraints. By identifying and selecting other carboxylase enzymes capable of reacting with CO?, they optimized the sequence of the pathway and minimized adverse side reactions through metabolic proofreading, which involves using additional enzymes to eliminate toxic byproducts.
Although this approach was reductionist and conducted in vitro (meaning it doesn't reflect how the pathway will behave in live organisms), it demonstrates the potential for engineered enzyme pathways to improve productivity. While the complexity of integrating such a system into living cells—and ultimately multicellular organisms like plants—remains a challenge, the implications for agriculture are significant.
2. Synthetic Immunology: Enhancing Immune Cell Capabilities
Immune cells are crucial for combating diseases and infections. Despite their remarkable capabilities, including the destruction of harmful cells and the production of signaling compounds, these cells face limitations. A review by Kole T. Roybal and Wendell A. Lim in the Annual Review of Immunology evaluated methods to engineer immune cells to better tackle complex diseases like cancer and autoimmune disorders.
In one experiment, researchers engineered a cytokine associated with T-cell growth, creating a variant called "superkine" or "Super-2." This modified cytokine no longer required a limiting subunit, allowing for enhanced T-cell activation and growth, even in the presence of immune suppressants—an important factor, as cancer cells can effectively suppress immune responses.
These studies exemplify how biological engineering can enhance existing processes and create new capabilities. As our understanding of biological systems deepens, we can develop innovative tools to navigate and overcome natural constraints.
Applications and Implications — The Relevance of Synthetic Biology
Tobias J. Erb et al. published a comprehensive article in 2017 that highlights the applications of metabolic engineering. By examining natural metabolic processes and studying known enzymes, we can learn to repurpose these enzymes, combine them in novel ways, and potentially develop entirely new enzymes. This principle applies to other proteins and biological components as well.
By addressing constraints in biological systems, we move closer to utilizing synthetic biology as a means to achieve a more sustainable future. From enhancing agricultural practices to reducing reliance on fossil fuels for everyday compounds, every step forward in understanding and engineering biology is crucial.
Further Reading on Synthetic Biology:
- SynBio at the World Economic Forum GTGS2021
- Synbiobeta — Leading Source for News, Trends, and Analysis
- The Second Decade of Synthetic Biology on Nature Communications
- NIH Synthetic Biology, including ethical considerations
Dami Adebajo recently completed a Bachelor’s in Biochemistry with a French Minor at the University of Waterloo, Canada. She plans to pursue a Master's in Applied Science in Biochemical Engineering. Her interests extend beyond biochemistry to language and linguistics, exploring how these fields shape our world. She is keen on delving into complex questions surrounding science, technology, and innovation.
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