Metabolic engineering may allow propane gas to be produced

 

The factory workers of tomorrow will work 24 hours a day in 37° heat, with minimal nutrition and certainly without pay. Unacceptable? On the contrary, these are ideal conditions for growing the microscopic workers at the centre of a manufacturing revolution.

Admittedly they won’t be churning out the latest cars or furnishing the new IKEA catalogue, but we are already using yeast and bacteria to make valuable chemicals. Recently the antimalarial drug artemisinin has been produced using yeast to make most of the structure and then add the last few parts on ourselves. This semi-synthetic approach is becoming more prevalent in the pharmaceutical industry.

Another target market for cell factories is the energy sector. News reports frequently warn of the impending exhaustion of fossil fuel supplies and the hazards involved in obtaining them – from oil spills to fracking tremors.

Scientists are using bacteria to tackle this fuel shortage. A particularly promising idea is to use cyanobacteria; microorganisms which use the same photosynthesis process as plants to make energy. They can then harness this solar energy to make specific fuels similar to the petrol in your car engine.

Fuels have much more simple chemical structures than complicated pharmaceuticals. You might think that would mean they are easier to make. You might be wrong. If cells don’t already produce similar products it takes a lot more tampering with the parts to get the machine to work. A combination of processes called metabolic engineering and directed evolution can expand the range of products available.

Metabolic engineering involves inserting the code for entire new functions into the cell’s DNA. This leads to the production of new proteins called enzymes which allow chemical reactions to occur. Picture a large map similar to the London Underground. Each line on the tube map is a metabolic pathway. Lines share stations and passengers in the same way pathways share enzymes and chemicals. A chemical moves along from enzyme to enzyme being modified until it reaches its destination – at which point it exits the system.

If you want to add a new enzyme to the cell it’s like adding a station to the map and building a new line to deliver chemicals to it. You might already use some of the established network and modify it, or alternatively build a whole new line of enzymes to work together. Now imagine you want to introduce a new station and deliver as many passengers from Victoria as possible, are there potential problems? Firstly, what about all the other stations that already receive passengers from Victoria? They might divert passengers away from our new station, but if we shut them down the whole network might collapse.

Then you must consider what happens to the chemicals when they reach the new enzyme station. Where do they all go once they are finished processing? Getting the chemical out of the cell once it has been made can be a problem – if it’s not secreted, difficult purification can be needed. If the product or by-products of the reaction are toxic the cells might stop working altogether. For example, if ethanol was a by-product of our new enzyme the cell factories would shut down pretty quickly – similar to the 5pm Friday work place exodus.

Metabolic engineering has already allowed hydrogen gas to be produced and work is currently underway to produce propane. Both of these are small enough to exit the cell. without the help of a specialist transport system.

The second process in designing our production line controls the fine tuning of the product. Directed evolution is like renovating the enzymes to make them specific for one type of chemical over another. This involves systematically altering the genetic code to change the protein structure. Very small changes can have large effects, often stopping the enzyme from working at all. However very selective enzymes can be developed with a high rate of production.

Many fuels come from crude oil. This is a mixture of chains of carbon atoms of varying lengths: petrol is longer than barbeque gas but shorter than jet fuel. Large refineries heat the oil up until each fraction has boiled off separately. Wouldn’t it be better if we could just use the combo of metabolic engineering and directed evolution to generate the desired carbon chain length with a specific enzyme? One enzyme could be evolved into a family of enzymes, each producing a different fuel. This would be more environmentally friendly and production would be easier to adjust in line with the demand for different chain lengths.

At the moment this technology is very much in its infancy. Once a pathway is in place the biggest challenge will be scaling the production up and making it energy efficient. Until that day comes we’d better get on our bike!

 

Philip Morrison