Applications of Synthetic Biology for Emerging Biotechnology

As government and corporate policies transition to meet the UNs sustainable development goals as outlined in Agenda 20301, there will be a drastic need for the invention and refinement of “green technologies” applicable in a variety of economic sectors and disciplines. Biotechnology has become heavily influenced by the field of synthetic biology2, which offers the capacity to deconstruct, shape, and rebuild natural systems from all domains of life. This is achieved via the development and integration of novel synthetic systems with natural biological processes. The potential of synthetic biology is now being realized as demonstrated by its application in numerous industries including (but not limited to): medicine3, agriculture4, food5, energy6 (both bio and petroleum based), natural product discovery and production7, pharmaceutical drug development8, and materials science9. Tools such as CRISPR-Cas910, along with the development of next generation DNA synthesis11, assembly12, and sequencing technologies13, have unlocked the potential of synthetic biology. This has made the engineering and augmentation of most living systems possible, allowing for the development of complex and refined genetically modified organisms (GMOs) for deployment in numerous applications. The world is transitioning into the era of the Fourth Industrial Revolution14, an era focused on the mitigation of climate change and the race to Net Zero15. I envision that synthetic biology will play a crucial role in this transition, and while this space is much too vast for one person to explore in totality, scientists continue to work on independent components while exploring collaboration for the synergistic application of their discoveries. Eventually, the input from varying specialties form functional “high-level” systems developed with synthetic biology. In particular, the fields of synthetic plant biology and synthetic yeast biology have shown great promise for the development of breakthrough biotechnology platforms. The engineering of plants that serve as primary feedstocks for biofuel production (which generally has focused on maximizing the feedstock-to-fuel conversion efficiency through cell wall engineering) is now exploring the augmentation of current agricultural systems for the bioproduction of high-value biologics and therapeutics in planta. While still nascent in application, there is much promise for these technologies due to the scalability of in planta production, without the need for sterile conditions or complex manufacturing controls. The development of more efficient and versatile methods for the engineering of synthetic genetic circuits in plants is crucial for the deployment of the highly specialized plant chassis in biotechnological settings. Yeast, on the other hand, can serve as a counterpart to large-scale bioproduction in plants by providing a chassis for biochemical pathway discovery and complete biosynthesis of complex molecules from all domains of life. Yeast is a highly dynamic single-celled eukaryotic organism that has been highly characterized and is easily manipulated/engineered in the lab. In recent decades yeast has proven to be an effective platform for the bioproduction of various natural, specialty, and commodity chemicals whose manufacturing is not possible or cost effective with current methods. Additionally, yeast as a bioproduction platform offers the prospective of new-to-nature molecules through the coalescing of biosynthetic enzymes from disparate pathways. This is a truly exciting prospect for the future of drug discovery and development as we utilize the vast genetic diversity of the biological world for the construction of novel biosynthetic enzymes and pathways. The following sections aim to highlight my research focused on synthetic plant and yeast biology, with a focus on the development of technologies and strategies for application in the bioenergy and bioproduction sectors. While this alone will not answer all the existential problems of a transitioning world, it represents a small piece of a very large puzzle that we as a collective are working to solve.

Advisor: Keasling, Jay D
Scheller, Henrik V