Science Literature

The claim that Rubisco is poorly designed or unintelligently designed was appearing in textbooks in the 1990s. The idea has been picked up recently in a News & Views piece by John Ellis. He writes that Rubisco "is a relic of a bygone age" and his essay has the title: "Tackling unintelligent design".

"Rubisco is the most important enyzme on the planet - virtually all the organic carbon in the biosphere derives ultimately from the carbon dioxide that this enzyme fixes from the atmosphere. But Rubisco is also one of the most inefficient enzymes on the planet. It evolved when the atmospheric composition was different from that of today, and its failure to adapt significantly to the modern atmosphere limits agricultural productivity."

RuBisCO has an active site (binding pocket) that binds ribulose-1,5-bisphosphate (RuBP) and catalyzes the reaction between RuBP and CO2 or O2. In the figure, the two large RuBisCO subunits (blue and cyan) sandwich an RuBP molecule (orange) in the active site. The site is gated by the C-terminus (yellow), lysine 128 (purple), and loop 6 (green), which undergo periodic conformational changes that open or close the site. Reactants enter and products escape while it is in an open state, and carbon-fixation reactions occur during the closed state. (Image credit: Paul Crozier, Sandia National Labs. Source here)

Over the past decade, the pendulum has swung away from the idea that Rubisco is unintelligent design. Its achievements are remarkable, as Griffiths (2006) explains:

"It is curious that Rubisco should fix CO2 at all, as there is 25 times more O2 than CO2 in solution at 25 degC, and a 500-fold difference between them in gaseous form. Yet only 25% of reactions are oxygenase events at this temperature, and carbon intermediates 'lost' to the carbon fixation reactions by oxygenase action are metabolized and partly recovered by the so-called photorespiratory pathway. Catalysis begins with activation of Rubisco by the enzyme Rubisco activase, when first CO2 and then a magnesium ion bind to the active site. The substrate, ribulose bisphosphate, then reacts with these to form an enediol intermediate, which engages with either another CO2 or an O2 molecule, either of which must diffuse down a solvent channel to reach the active site."

The analysis of Tcherkez et al. (2006) was significant for showing that Rubisco does not bear the marks of Darwinian tinkering and that research to genetic modify the enzyme to gain agricultural benefits can be expected to deliver only "modest improvements" in its efficiency of operation.

"Further, [our hypothesis] raises the possibility that, despite appearing sluggish and confused, most Rubiscos may be near-optimally adapted to their different gaseous and thermal environments. If so, genetic manipulation can be expected to achieve only modest improvements in the efficiency of Rubisco and plant growth. Such improvement would be limited to the magnitude of the scatter apparent in the correlations (Fig. 3), if the scatter represents incomplete optimization (see above). [. . .] Such adaptation in response to the changing atmosphere and temperature appears to have been instrumental in enabling the expansion of the biosphere to its current size."

Design theorists have drawn attention to three additional considerations:
1. A single-factor analysis of Rubisco is inadequate. The parameters considered to conclude the enzyme is poorly designed and inefficient are very limited. We should note that our perceptions of intelligent design are typically subjective, and most claims for poor design do not stand up to the test of time - further research leads to a greater appreciation of design (a good example being mammalian eye design). Furthermore, unintelligent design of architectures we deem sub-optimal should not be regarded as the only possible hypothesis. Multiple factors are likely to be relevant as chemosynthetic carbon fixation also makes use of Rubisco. It is employed by organisms living at hydrothermal vents and cold hydrocarbon seeps.
2. Photorespiration, the consumption of oxygen to produce a sugar that ultimately forms carbon dioxide during a series of reactions, may not be a mark of inefficiency, but the process may be useful to the plant. The null hypothesis for Design theorists is that processes have functionality. This hypothesis is not without some support: the process of photosynthesis is not just to capture CO2 and release oxygen because nitrate assimilation in plant shoots depends on photorespiration, as Rachmilevitch et al (2004) have shown.
3. Ecological considerations should be included in the analysis. If design is relevant to understanding the way plants work, we should consider not only the benefits to the organism (which limits the horizon for those with a Darwinian perspective) but also the biosphere as a whole. Rubisco's ability to capture CO2 increases with increasing CO2 content in the atmosphere, so its efficiency rises in a CO2-rich atmosphere. However, increasing oxygen levels in the atmosphere will reduce Rubisco's ability to capture carbon. So a negative feedback mechanism exists to regulate the relative concentrations of oxygen and carbon dioxide in the atmosphere. This is another example of design affecting the Earth's ecology - for more on this, go here.

Ellis was commenting on a paper by Liu et al. that reports on work to produce a Rubisco in vitro. In order to do this, the authors required two chaperone proteins, ATP and addition of 18 protein subunits (taken from a cyanobacterial Rubisco) to be introduced in the correct sequence to get yields of the enzyme. It is hoped that this procedure can be used to produce mutated versions that can be screened for improved effectiveness. It's all very interesting, but the biggest mystery is why people who expend so much intellectual energy on improving this remarkable molecule can live with the thought that "Rubisco is a superb example of unintelligent design for the modern world". Maybe research funds would be better spent exploring avenues identified using the presumption that this enzyme is optimally designed.

Tackling unintelligent design
R. John Ellis
Nature 463, 164-165 (14 January 2010) | doi:10.1038/463164a [restricted link]

Abstract: The key enzyme in photosynthesis, Rubisco, is a relic of a bygone age. The ability to assemble Rubisco in the test tube offers the prospect of genetically manipulating the enzyme to make it fit for the modern world.

Coupled chaperone action in folding and assembly of hexadecameric Rubisco
Cuimin Liu, Anna L. Young, Amanda Starling-Windhof, Andreas Bracher, Sandra Saschenbrecker, Bharathi Vasudeva Rao, Karnam Vasudeva Rao, Otto Berninghausen, Thorsten Mielke, F. Ulrich Hartl, Roland Beckmann & Manajit Hayer-Hartl.
Nature 463, 197-202 (14 January 2010) | doi:10.1038/nature08651 [restricted link]

Abstract: Form I Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase), a complex of eight large (RbcL) and eight small (RbcS) subunits, catalyses the fixation of atmospheric CO2 in photosynthesis. The limited catalytic efficiency of Rubisco has sparked extensive efforts to re-engineer the enzyme with the goal of enhancing agricultural productivity. To facilitate such efforts we analysed the formation of cyanobacterial form I Rubisco by in vitro reconstitution and cryo-electron microscopy. We show that RbcL subunit folding by the GroEL/GroES chaperonin is tightly coupled with assembly mediated by the chaperone RbcX2. RbcL monomers remain partially unstable and retain high affinity for GroEL until captured by RbcX2. As revealed by the structure of a RbcL8-(RbcX2)8 assembly intermediate, RbcX2 acts as a molecular staple in stabilizing the RbcL subunits as dimers and facilitates RbcL8 core assembly. Finally, addition of RbcS results in RbcX2 release and holoenzyme formation. Specific assembly chaperones may be required more generally in the formation of complex oligomeric structures when folding is closely coupled to assembly.

See also:

Griffiths, H., Designs on Rubisco, Nature 441, 940-941 (22 June 2006) | doi:10.1038/441940a [restricted link]

Rachmilevitch, S., Cousins, A.B., Bloom, A.J., 2004. Nitrate Assimilation in plant shoots depends on photorespiration. Proceedings of the National Academy of Sciences USA, 101(31), 11506-11510 | doi: 10.1073/pnas.0404388101 [abstract]

Tcherkez, G.G.B., Farquhar, G.D. and Andrews, T.J., Despite slow catalysis and confused substrate specificity, all ribulose bisphosphate carboxylases may be nearly perfectly optimized, Proceedings of the National Academy of Sciences USA, May 9, 2006, 103(19), 7246-7251 | doi: 10.1073/pnas.0600605103 [abstract]