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Transforming the future of agriculture through synthetic photorespiration

Periodic Reporting for period 4 - FutureAgriculture (Transforming the future of agriculture through synthetic photorespiration)

Reporting period: 2019-07-01 to 2021-03-31

Carbon fixation is the most important biological processes on earth, supporting our biosphere by transforming inorganic carbon into organic matter and literally feeding all life forms. The Calvin–Benson–Bassham Cycle (CBBC or Calvin cycle) – operating in higher plants, algae, and many bacteria – is responsible for ≥ 95% of the carbon fixed in the biosphere. Despite being under a strong selective pressure for eons, the Calvin cycle still displays inefficiencies related to the enzymes it employs; especially one of its key enzymes, the carboxylating enzyme RuBisCO, is inefficient. RuBisCO is very slow and cannot fully distinguish between CO2 and molecular oxygen. When oxygen replaces CO2 as substrate for RuBisCO’s activity, a toxic waste product, 2-phosphoglycolate (2PG), is produced. 2PG must be recycled back into the Calvin cycle via a process termed photorespiration. However, plant photorespiration dissipates energy and releases CO2, thereby directly counteracting the function of RuBisCO, reducing the effective rate of carbon fixation, and lowering agricultural productivity.
FutureAgriculture aims to boost agricultural productivity by designing and engineering plants that directly overcome the deficits of natural photorespiration and that support higher photosynthetic rate and yield. Alternative metabolic pathways that can bypass photorespiration without releasing CO2 are screened in silico by taking into account all known enzymes, as well as enzymes that could be easily evolved from them. The synthetic enzymes are integrated with existing ones to obtain entirely new pathways optimized by chemical logic, which will, in turn, be realized in vitro and then in vivo within bacteria and plants. Their implementation in plants is expected to significantly increase plant growth rate and biomass yield under various environmental conditions. This will provide the basis for increasing agricultural productivity of the crops that comprise >60% of agricultural production, including rice, wheat, barley, oat, soybean, cotton, and potato.
Using state-of-the-art synthetic biology tools, the project team set out to design and engineer entirely new photorespiration pathways that do not release CO2 or would even be able to capture additional CO2. Using computer simulations, we demonstrated that certain bypass routes could dramatically boost the agricultural productivity rate potentially by as much as 60 %, and would also be able to support higher yields in a wide variety of conditions, such as drought, poor light, which are a challenge for plants in their natural environment. The analysis was published in PNAS in 2019 and received much attention. The project identified both pathways that included known enzymes, which seem to be very promising, but also new pathways based on enzymes, not known to nature yet. In FUTUREAGRICULTURE, we set out to engineer these new solutions. One of the most promising designs is the so-called tartronyl-CoA (TaCo) pathway. The greatest benefit of the TaCo pathway is that it fixes CO2 instead of releasing it, as it happens in natural photorespiration. As a result, the TaCo pathway is more energy-efficient than any other proposed photorespiratory bypass to date. Enhanced photosynthetic efficiency of the TaCo pathway has recently been demonstrated in vitro by the consortium and was reported in Nature Catalysis.
The TaCo pathway has already been partially realized in cyanobacteria (photosynthetic bacteria living in the soil and water) and also been implemented in model plants, some of them showing a significant physiological advantage compared to wild-type plants when grown under extreme drought conditions, which enhances photorespiration. The FUTUREAGRICULTURE team is now validating the results in plants and planning to transfer them to major crops.
These promising results provide hope that the new pathways developed in FUTUREAGRICULTURE perform similarly well under difficult or challenging conditions in the field because they are much more CO2 efficient. It is expected that plants with the new pathways are more tolerant to the lack of water and produce more biomass per unit of land and of time than at present.
Feeding 10-15 billion people in the year 2100 is a challenging task that will only be met by drastic measures to increase agricultural productivity. But if we are to maintain our natural biodiversity and habitat, we cannot continue to expand arable lands. Climate change will impact the future of agriculture in a complex multifaceted way. According to some simulations, a drop in yields and nutrients can be expected according to different latitudes. Even more, land suitability maps will change worldwide, disrupting current local agricultural economies and value chains with detrimental effects on agricultural product prices. This means that we must find new ways to boost the productivity of food crops within the existing space available and in a wide range of conditions, including the growing impact of climate change and associated droughts and floods.

Along these lines, FutureAgriculture offers not an incremental improvement but rather a leap in agricultural productivity. Most other research efforts that aim to improve photosynthetic yield involve enormous implementation barriers. In contrast, FutureAgriculture’s engineering aims can be achieved within a reasonable timeframe as they are strictly genetic/metabolic and do not involve morphological or any other structural modifications. Hence, the development and implementation of synthetic photorespiration routes can transform the future of agriculture.
Furthermore, while the improvement of photosynthetic rate and yield via transgenic approaches has been a hot research topic for many years, these efforts focused on introducing existing pathways into new plant hosts. FutureAgriculture adopts a radically different approach. Rather than reshuffling and grafting existing enzymes in a fashion that resembles natural evolution and is in line with current metabolic-engineering thinking, the project systematically explores novel pathways that cannot be obtained by mixing and matching of existing, natural enzymes. FutureAgriculture’s approach demands the de novo engineering of new enzymes to catalyze metabolic transformations that are unknown in nature. These synthetic enzymes are integrated with existing ones to obtain entirely new pathways optimized by chemical logic, which will in turn be realized within bacteria and plants. Given the combinatorial nature of metabolic pathways, the addition of only one novel reaction dramatically expands the solution space of possible pathways, thus fully realizing the potential of synthetic biology. Yet, so far, only a handful of studies implemented synthetic pathways that harbor novel enzymes. FutureAgriculture takes this strategy to a new level by constructing de novo pathways within the very core of carbon metabolism.
Schematic illustration of the beneficial effects in the engineered plants