Building better biology

June 7, 2010 § 3 Comments

The very first paper from Ron Milo’s lab (Bar-Even A, Noor E, Lewis NE, Milo R. Design and analysis of synthetic carbon fixation pathways. Proc Natl Acad Sci U S A. 2010 107 8889-94. PMID: 20410460)  is out in PNAS — congratulations, Ron!

This is a nicely done theoretical/computational study asking whether it is possible to increase the overall efficiency of photosynthesis.  People have tried to increase the efficiency of RuBisCo, the primary enzyme that performs the carbon fixation step but unsurprisingly (well, I’m not surprised, don’t know about you) this turns out to be hard.   Bar-Even et al. point out that there are many different carbon fixation strategies in nature, and in a gedankenexperiment we might call “virtual gene shuffling” they ask whether one could re-assort naturally occuring enzymes from different pathways to create a new, hybrid pathway with better efficiency.

How can you ask this question in a meaningful way? It isn’t trivial. It’s not enough to have a pathway that can fix carbon faster (although faster fixation is good); you also have to balance factors such as the total amount of protein the cell needs to make to create a functional pathway, and how much cellular energy the pathway consumes to make the product.  The need to minimize energy consumption is complicated by the fact that fixing carbon is thermodynamically unfavorable, so there’s a lower limit of energy input (ATP hydrolysis) that is absolutely required to make the reaction go. Interestingly, one significant factor is the choice of electron acceptor in the pathway, since recycling NAD(P)H or ferredoxin is more efficient than recycling FAD or ubiquinone.

An early step that helped to narrow the search space was to compare the characteristics of the central enzymes in the pathway, the carbon-fixing enzymes. The clear winner here was PEP carboxylase, with a specific activity of almost 20x that of RuBisCo at ambient levels of carbon dioxide; pyruvate carboxylase came in at second place. Bar-Even et al. then looked for optimized cycles (short, fast, chemically reasonable cycles) that used the carbon-fixing enzymes with the best characteristics. To do this, they had to pull together information on kinetics for all the 5,000 enzymes they wanted to test in these networks — a heroic task that must have led to a lot of new entries into BioNumbers. They find several pathways that look as if they should be up to 3x more efficient than natural pathways, and use an existing model of carbon metabolism in Chlamydomonas to test whether these proposed pathways could actually function to support growth in a real organism.  And they look as though they can.

So what I want to know now is — are you building it, Ron? If not, I think Craig Venter may need something new to do.

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§ 3 Responses to Building better biology

  • Bodo Stern says:

    A recent paper in Science argues that increased carbon fixation through RUBISCO does not lead to increased plant growth since nitrogen assimilation is reduced. The authors propose that photo-oxidation, the apparently evil side-reaction of RUBISCO which uses oxygen instead of carbon dioxide, may actually promote nitrogen assimilation. Those results don’t argue against improving carbon fixation with carbon fixing enzymes like PEP carboxylase a la Bar-Even et al. but I think they put a damper on those approaches that try to improve RUBISCO’s itself.

    paper: Carbon Dioxide Enrichment Inhibits Nitrate Assimilation in Wheat and Arabidopsis
    Arnold J. Bloom,* Martin Burger, Jose Salvador Rubio Asensio, Asaph B. Cousins
    The concentration of carbon dioxide in Earth’s atmosphere may double by the end of the 21st century. The response of higher plants to a carbon dioxide doubling often includes a decline in their nitrogen status, but the reasons for this decline have been uncertain. We used five independent methods with wheat and Arabidopsis to show that atmospheric carbon dioxide enrichment inhibited the assimilation of nitrate into organic nitrogen compounds. This inhibition may be largely responsible for carbon dioxide acclimation, the decrease in photosynthesis and growth of plants conducting C3 carbon fixation after long exposures (days to years) to carbon dioxide enrichment. These results suggest that the relative availability of soil ammonium and nitrate to most plants will become increasingly important in determining their productivity as well as their quality as food.

  • Ron Milo says:

    Plants are walking (standing?) on a tight rope of limiting factors for growth (probably all other organisms as well…). Carbon, nitrogen, water etc are showing strong inter dependencies (and thanks Bodo for this new paper I didn’t see before). For example, I was struck when I learnt that to fix 1 kg of carbon you need to evaporate ~300 kg of water by necessity because the atmosphere is actually so carbon dioxide rare in comparison to water vapor in the leaf. In agriculture we are able to push the limits beyond what we find in most natural conditions by supplying nutrients, defending from pests etc. We are effectively trying to optimize productivity by artificially solving for plants some of the things they needed to cope with in evolution. But we need a better understanding fast to have some new productivity nails to keep Malthus in the coffin as his predictions are getting close…

  • Dave Savage says:

    Yes, the general consensus does seem to be the rubisco has optimally evolved in the context of its particular host. What I find really intriguing about Ron’s work here and in a related paper with the Tlusty lab (Savir et al. PNAS 2010), which defines the evolutionary adaptation of rubisco enzymes across species, is that we now have an experimental metabolic toolbox for testing hypotheses about the environmental constraints that shaped carbon-fixing organisms. E.g. is there really a fundamental link between N and C or is this merely an environmental consequence that agriculture will compensate for? What a cool system. Not all enzyme active sites get to terraform a planet!

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