Item type:Thesis, Open Access

Establishing the Chlamydomonas reinhardtii chloroplast as a platform for photosynthesis engineering

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Philipps-Universität Marburg

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Abstract

The detrimental effects of human activities on the environment have been clearly documented, leading to a global effort to curb industrial pollution and decrease energy consumption. Human-generated pollutants, especially carbon dioxide (CO2), play a significant role in atmospheric degradation. The dramatic increase in industrial CO2 emissions over the centuries has resulted in a concerning accumulation in the atmosphere, adversely affecting human health and ecosystem stability. Despite this, CO2 is vital for phototrophic organisms like plants, algae, and cyanobacteria, which utilize CO2 and use the carbon to create organic molecules through photosynthesis. With its unique capacity to convert light energy into inorganic carbon assimilation, it has been a central subject of scientific research, offering substantial potential for fields such as agronomy and energy production, alongside fundamental studies. Enhancing photosynthesis is a complex challenge that demands a deep understanding of its mechanisms and the creation of advanced tools for practical use. This thesis seeks to dive into into the complexities of improving photosynthetic efficiency, employing innovative methodologies from synthetic biology to enhance our comprehension and application of this essential biological process. The aim is to establish Chlamydomonas reinhardtii as a chassis for carbon fixation engineering, through the development of new tools to engineer the plastome. This should be implemented using a proof of concept photorespiratory bypass in the chloroplast of C. reinhardtii and its characterization, and by relocating the small subunit of Rubisco rbcS from the nuclear genome to the chloroplast genome. This should contribute to fortifying the chloroplast genome of C. reinhardtii as a suitable testing ground for complex endeavors, while remaining translatable to higher plants through the conservation of chloroplasts throughout the tree of life. In the first part of the thesis we show the construction of a MoClo toolkit for the chloroplast genome of C. reinhardtii, through the establishment of high-throughput part characterization pipeline. This allowed us to screen for more than 300 parts, including untranslated regions (UTRs) and promoters. By testing unique combination of regulatory elements, we identified two transcritpion units suited for the implementation of the South pathway as a photorespiratory bypass. The pathway is constituted of two genes, a glycolate dehydrogenase and a malate synthase, that were assembled in the characterized transcription units. These transgenes were transformed in the chloroplast of a characterized mutant strain displaying increased photorespiration. Through genomic, proteomic, metabolomic and phenotypic characterization in photorespiratory conditions, we show the successful implementation of the pathway. Transplastomic strains displayed reduced doubling time and final cell density compared to the mutant strains, explained by lower intermediates of natural photorespiration suggesting an increased flux in the bypass. Finally, we set out to re-localize the small subunit of Rubisco from the nuclear genome to the chloroplast genome, by transforming the endogenous Crrbcs1 gene in the chloroplast of mutant strain for rbcS and the pyrenoid. Though the knock-out strain does not behave as expected and maintains growth in minimal phototrophic conditions, the presence of the transgene was confirmed and a drastic impact on growth and cell density was exhibited in the transplastomic strain, reducing its doubling time by three compared to the mutant and reaching cell densities comparable to wild-type levels. Overall in this thesis, I have establish the basic tools and proofs of concept to use the chloroplast of C. reinhardtii as a testbed for photosynthesis engineering. By showing that we can engineer a photorespiratory bypass and re-localize the small subunit of Rubisco in the chloroplast genome, we now open the possibility of testing multiple pathways, cycles and variants in a high-throughput manner, using the established pipeline and characterized mutants.

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Chotel, Tanguy (0009-0001-4723-7588): Establishing the Chlamydomonas reinhardtii chloroplast as a platform for photosynthesis engineering. : Philipps-Universität Marburg 2025-02-12. DOI: https://doi.org/10.17192/z2025.0047.