Using Synthetic Biology to Produce High-Value Diterpenoids in Chlamydomonas Reinhardtii

The demand for food, fuel and pharmaceuticals by an ever-growing world population is fast outstripping sustainable supply. Adoption of industrial biotechnology platforms for synthesis of high-value and high-demand products provides a means to improve the sustainable supply bottleneck. While large-scale bacterial and yeast platforms are mature industries, there are biological constraints on the range of molecules that can be synthesised by these organisms. Photosynthetic algal platforms are capable of production of diverse and complex compounds, including vitamins such as carotenoids (pro-vitamin A), oils (such as omega-3 fatty acids), and by genetic manipulation, novel compounds for pharmaceuticals, such as plant natural products or glycosylated antigens. However, despite some success stories, the low yields reported for many target products are a major obstacle to up-scaling and commercial viability of algal platforms.

We have exploited the green microalga, Chlamydomonas reinhardtii, as a chassis organism for scalable and high-throughput production of medicinal compounds. We are taking a synthetic biology driven approach, following the principle of design, build, and test to overcome the scalability constraints associated with first-generation engineered algal platforms. Using functionally defined standardised parts and workflows, we are able to predictably generate C. reinhardtii strains that efficiently express multiple heterologous genes. For control of transgene expression, we have developed a versatile and easily regulated system based on thiamine-pyrophosphate riboswitches, which are responsive to the concentration of thiamine and its analogues in the growth medium. Using these strategies and molecular resources we are engineering C. reinhardtii for scalable production of diterpenoids with medicinal properties.

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Keyword
Synthetic biology, metabolic engineering, microalgae, riboswitch, diterpenoids