Water would suck in this regard.
Of course. But mostly it is this, the rest can be either worked around or taken into account and designed to not be needed or methods can be added to handle it.
Folding is for the proteins; when it is critical, you have to encode also the chaperones to assist its folding. Methylation is for regulation of transcription of DNA, AFAIK, and that’s either unused in the proposed applications or also can be handled.
I assume a good part of it will be determined genetically and epigenetically. Then there are the other factors, like the current state of the body and other chemicals present that may tie down the enzymes (see e.g. the grape juice effects on the CP450s…)… We need easy and cheap analytical techniques for close monitoring…
