[lblume]

I once visited a lab near Berlin where they told me that cell-free synthesis is basically like cell-based synthesis, just that they kill the cells first and use what's inside. The major benefit, I was told, was that you don't have to keep the cells alive.

It sounds very odd at first glance but seems very fascinating to me (and I know way less about biology than I would like to), this idea of dissecting a system into its pieces because we know how to use the pieces in a superior way to the original system itself.

[asdff]

Think of it more as just getting to the one function that you are using. I think a cell free technique that people might have heard of even in high school biology at this point is the polymerase chain reaction. Rather than have some cell we grow in some growth media under certain conditions optimal for cell growth and harvest cloned DNA from these cells, we have isolated the involved protein directly (DNA Polymerase). We know exactly what temperature is most optimal for each step, and infact depending on what targets of DNA we are looking at certain temperatures may be more optimal for these targets. We know the exact pH that these molecules are most effective at and this might not even be a pH found in the cell but one determined empirically by measuring enzyme activity across a gradient of pH and/or temperature ranges among other potential conditions. We know the inputs and reaction and can supply just enough of these molecules as we need to drive satisfactory yield in order to decrease our costs. We can optimize the timing of this temperature-dependent reaction again to the specifics of the DNA molecule that we are amplifying. We can change how quickly this reaction is heated up or cooled down to optimize for product yield. We can change out components of this reaction such as our enzyme for ones that might operate faster with less accuracy, or ones that operate slower with higher fidelity, or ones found from other species that might have these properties, or engineered proteins that might have these properties.

Many reasons why you'd want to go cell free. You are no longer binned into the cell but are now just throwing things into a tube where you can control all the parameters that matter for your desired function.

[tomohelix]

I don't like that description very much. The cell being "alive" is literally the top reason the cellular machineries work so well. By being "alive" it is keeping the environment optimal and perfect for the enzymes to run and being productive. Taking this away and then seeing problems about efficiency is like taking off the wheels and then asking why the car is not running well.

They are trying to fix it by maintaining the same cytoplasmic conditions using all the machines and sensors in a bioreactor. But that can scale is a different question. The narrow ranges of conditions biological processes require is already hard to maintain while the cells itself is still whole and using more than half of its enzymes to do this.

[veunes]

Biology really is the ultimate modular system!