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.