Although Nature titled this piece “Tackling Unintelligent Design” they betray their own bias and fail to appreciate the irony in their claims.
According to R. John Ellis from the University of Warwick “Rubisco, the key enzyme in photosynthesis, is a relic of a bygone age.”
Researchers now plan to genetically manipulate the enzyme to make a designer enzyme fit for the modern world.
Although Rubisco is the most important enyzme on the planet, it is also one of the most inefficient. It evolved when the atmosphere was different and failed to adapt to the modern atmosphere. Attempts to improve the properties of this key enzyme of plants and cyanobacteria have failed because it proved impossible to reconstitute Rubisco in vitro. Liu et al. (Nature 463, 197–202 (2010) Vol 463 14 January 2010 doi:10.1038/nature08651) have overcome this problem with a cyanobacterial Rubisco by using two different chaperone proteins, which guide the folding and assembly of the enzyme.
Ribulose 1,5- bisphosphate carboxylase/oxygenase, reacts with either CO2 or oxygen. The reaction with oxygen competes with the carboxylation reaction in which CO2 is fixed, and feeds a pathway called photorespiration that is peculiar to plants. Photo respiration causes the loss of up to 25% of the carbon that is fixed by the carboxylation reaction.
Rubisco is near the bottom of the league table of enzyme efficiency, with a catalytic rate of only three to ten molecules of CO2 fixed per second per molecule of enzyme. This inefficiency explains why Rubisco is the most abundant protein in the world. To cap it all, the enzyme is not saturated at current levels of CO2 in the atmosphere, which is why some growers elevate this concentration inside their greenhouses. None of these deficiencies mattered when Rubisco first evolved, as there was no oxygen in the atmosphere and the level of CO2 was much higher than it is today.
Rubisco is a large oligomer, consisting of eight catalytic large subunits bound to eight structural small subunits. This is why plant Rubisco is one of the few proteins that has never been successfully reconstituted in vitro into an active enzyme from its unfolded subunits.
Molecular chaperones work by combating protein aggregation by binding to transiently exposed, interactive surfaces on individual protein chains at the stage of folding and/or assembly.
The protein that mediates Rubisco folding is called a chaperonin. They function by enclosing each individual folding chain inside a closed cavity, where the chain completes its folding into a monomer in the absence of other folding chains. The closing and opening of the cavity requires ATP — the molecular source of energy used by cells.
Liu et al. defined the conditions necessary for the formation of active enzyme in vitro from purified, unfolded large subunits and folded small subunits of a cyanobacterial Rubisco. First incubate unfolded large subunits with GroEL/ES, RbcX and ATP, to allow the large subunit to fold and bind to RbcX, then add folded small subunits to displace the RbcX and so bind the folded large subunits. RbcX chaperone acts as a ‘molecular staple’ that binds to partly folded large-subunit chains in such a way that they interact correctly with small subunits, rather than aggregating with one another.
The authors set up an in vitro system from which they obtained active Rubisco in yields up to 40% and can be used to screen the effects of mutations in the large-subunit chains in the hope of obtaining an improved enzyme.
Just how successful they will be in manipulating this brillianty molecule remains to be seen.