My first post may be considered a bit of a cheat as the subject is very closely related to my own research, but we have to start somewhere! This paper talks about how this group have changed the shape of an enzyme to change the way it works. The work all revolves around a chemical called perillyl alcohol which could be an effective anti-cancer drug. At the moment perillyl alcohol is purified from natural sources such as lavender oil and cherries but, as it is only there in very low levels, this is an expensive process. In order to make this chemical more feasible as a drug we need to come up with a cheap way of making loads of it. And the answer lies in enzymes.
For those of you who’ve forgotten high school biology, enzymes are proteins which catalyse reactions, which means they take a one chemical (called the substrate) and turn it into another (the product) millions of times faster than the same reaction would occur without the enzyme. Enzymes exist in all living systems; they are involved in making our cells, in breaking down our food…. without enzymes nothing would happen fast enough for life to exist! The bit you’ll probably remember about enzymes is that they are very specific, that is they will only bind substrates of a specific shape (lock & key model and all that). Depending on how the initial substrate binds you’ll then only get specific products released, and this is where the paper comes in.
They found an enzyme (with the great name of CYP102A1) which binds a substrate called limonene which can be very cheaply extracted at high levels from lemons. CYP102A1 converts limonene into a number of different products depending on how it binds the limonene. All of these products are very similar to our friend perillyl alcohol but with some key differences that mean they won’t work as an anti-cancer drug. The group of scientists therefore decided to examine, using some pretty swanky computer simulations, what it was about the shape of the binding site on CYP102A1 that meant it wouldn’t convert limonene into perillyl alcohol. Once they’d identified the important bits of the enzyme they changed them in various different ways and carried out some trials to see if the enzyme would now generate some perillyl alcohol when they fed it limonene. It took a couple of attempts but in the end they made three changes which meant the CYP102A1 now converts 97% of the limonene into perillyl alcohol and only 3% into other useless products. This is quite an achievement and now means that the enzyme could be used on an industrial scale to make bucket loads of perillyl alcohol which may one day help people suffering with cancer.