In a groundbreaking advance poised to transform the landscape of agricultural biotechnology, researchers have unveiled the cryogenic electron microscopy (cryo-EM) structure of the carbon dioxide (CO₂)-inducible bicarbonate channel LciA from the green alga Chlamydomonas reinhardtii. This discovery not only clarifies long-standing ambiguities about the molecular mechanism of LciA but also introduces innovative pathways to engineer proteins capable of boosting photosynthetic efficiency in C₃ crops — a critical leap toward meeting global food security in the face of climate change.
Photosynthesis in C₃ plants, which make up most of the world’s staple crops including rice, wheat, and soybeans, is fundamentally constrained by inefficient carbon capture. Unlike their counterparts, C₄ and certain algal species, C₃ plants lack sophisticated CO₂-concentrating mechanisms (CCMs) that enable the accumulation of inorganic carbon in the form of bicarbonate (HCO₃⁻) near the enzyme Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). This shortfall leads to suboptimal photosynthetic rates and significant losses in crop yield under ambient CO₂ conditions.
LciA is a chloroplast envelope transporter protein implicated in the algal CCM. It belongs to the formate/nitrite transporter (FNT) family, a group known for facilitating the movement of small anions across membranes. Despite LciA’s critical role in algal CO₂ concentration, translating its function to C₃ plants has been obstructed by incomplete structural and functional understanding. The novel cryo-EM structure elucidated by Guo et al. provides an atomically detailed view of LciA, illuminating the channel architecture and specific residues that define substrate selectivity and permeability.
This study reveals the intricate molecular choreography governing bicarbonate passage through LciA. The selectivity filter, essential for distinguishing bicarbonate from other anions, is fashioned by both electrostatic and steric factors. Positively charged residues, chiefly Lys220, create an electrostatic environment favoring bicarbonate coordination. In parallel, residues Ala117 and Val267 impose a steric constraint, deftly engineering a molecular sieve that fine-tunes substrate specificity. This dual mechanism underpins the channel’s remarkable ability to preferentially transport bicarbonate ions, an attribute essential for concentrating CO₂ inside the chloroplast.
Capitalizing on these structural insights, the researchers harnessed site-directed mutagenesis to enhance and modify function. Two substitutions, K136A and A114F, dramatically elevated LciA channel activity, which is a promising step toward more effective synthetic CCM deployment in crop plants. The ability to fine-tune such transport proteins could drastically improve bicarbonate influx, thereby augmenting the efficiency of downstream photosynthetic enzymes under CO₂-limited conditions.
Moreover, the research extends beyond LciA by exploring its evolutionary relatives within the FNT protein family. Through targeted engineering, the bacterial nitrite channel NirC was successfully reprogrammed to acquire bicarbonate transport capability. This finding suggests that the FNT family harbors latent potential to be transformed into bicarb transporters, broadening the toolkit for synthetic biology strategies aimed at enhancing photosynthesis.
The investigations also scrutinized the bicarbonate transport capacity of Chlamydomonas nitrite channels NAR1.1 and NAR1.5, both of which demonstrated inherent bicarbonate transport properties. Of significance is the prospect that like LciA and engineered NirC, these channels can be further optimized to bolster bicarbonate uptake in heterologous systems, presenting multiple nodes of intervention in engineering efficient CCM-like systems into C₃ crops.
By bridging structural biology and functional assays with rational protein design, this work forges a detailed blueprint for manipulating membrane transporters that control inorganic carbon flux. The implications resonate profoundly, offering a tangible molecular strategy to circumvent photosynthetic limitations faced by global agriculture amid rising atmospheric CO₂ and climate volatility.
Importantly, the ability to transplant and repurpose algal bicarbonate transport machinery into plants addresses a foundational bottleneck in synthetic biology approaches aiming to emulate algal CCMs. Existing efforts often grapple with the complex integration of multiple protein components and the challenge of achieving efficient bicarbonate transport across plant chloroplast envelopes. LciA, and its engineered homologs, now emerge as exemplars of functional modules that can be modularly introduced with predictable outcomes.
From an evolutionary perspective, this study underscores the plasticity of the FNT family and highlights evolutionary trajectories that can be exploited by modern protein engineering. It also reveals how subtle conformational dynamics and residue substitutions mediate functional shifts from nitrite to bicarbonate specificity — a remarkable demonstration of molecular adaptation with potent biotechnological ramifications.
The research has broader implications for understanding algae’s inherently superior carbon concentrating capabilities and empowering similar advances in terrestrial crops. Increased bicarbonate transport into chloroplasts would enhance CO₂ supply to Rubisco, potentially reducing photorespiration losses, increasing photosynthetic efficiency, and ultimately boosting crop yields under suboptimal CO₂ conditions.
This study also sets the stage for future exploration of synergistic CCM components, examining how combined expression of bicarbonate transporters, active inorganic carbon pumps, and specialized carbonic anhydrases can be orchestrated for optimal performance in synthetic plants. It brings us closer to a vision where tailored, high-efficiency CCMs can be integrated into staple crops to sustain a growing population.
The highly detailed cryo-EM structure of LciA represents a monumental technical achievement, offering atomic resolution maps that will support state-of-the-art computational modeling and targeted mutagenesis strategies. It invites a new era of precision engineering for membrane transport proteins that were previously understood only through indirect functional inferences.
In summary, the work by Guo and colleagues dramatically expands the molecular toolbox available for synthetic and systems biology interventions aimed at overcoming photosynthetic inefficiency. By establishing LciA as an archetypal bicarbonate channel and demonstrating the feasibility of tailoring FNT proteins for new substrate specificities, it lays a robust foundation for engineering enhanced photosynthetic systems in crops and algae alike.
As climate change pressures intensify and the demand for sustainable agricultural productivity escalates, innovations like these herald a transformative approach—leveraging fundamental structure-function insights to reimagine plant metabolism at the molecular level. Their impact promises to revolutionize how plants harness and concentrate CO₂, making this a pivotal step toward securing future food supplies and ecological stability.
The pioneering approach exemplified here, combining cryo-EM structural biology, mutagenesis-driven functional enhancement, and evolutionary protein reprogramming, will likely inspire further advances across membrane transporter research. Ultimately, it exemplifies how deep biochemical understanding can unlock new frontiers in crop improvement, signaling hope for resilient and highly productive agricultural ecosystems.
Subject of Research:
Structural biology and protein engineering of CO₂-concentrating mechanism components in algae and their application to enhance photosynthetic efficiency in C₃ crops.
Article Title:
Structure of Chlamydomonas reinhardtii LciA guided the engineering of FNT family proteins to gain bicarbonate transport activity.
Article References:
Guo, J., Yang, Z., Zhang, X. et al. Structure of Chlamydomonas reinhardtii LciA guided the engineering of FNT family proteins to gain bicarbonate transport activity. Nat. Plants (2026). https://doi.org/10.1038/s41477-025-02200-9
Image Credits: AI Generated
DOI:
https://doi.org/10.1038/s41477-025-02200-9
Tags: agricultural biotechnology advancementsbicarbonate transport proteinscarbon capture mechanisms in plantsChlamydomonas reinhardtii researchclimate change and food securityCO2-inducible bicarbonate channelscryogenic electron microscopy in agricultureengineering FNT proteins for crop improvementenhancing photosynthesis in C3 cropsimproving crop yield through biotechnologymolecular mechanisms of photosynthesisphotosynthetic efficiency in staple crops
