Seeing as there are e85 pumps relatively plentiful where I am, and I would be running an over drive trans I have considered making my project somewhat of a daily driver.
How stressful would this be on my engine running 12.5:1 to 13:1 compression and putting a considerable amount of mileage on it? Shouldn't be too bad should it?

 

With good cooling system I dont see a problem with it. 12.5 to 1 is doable with E85 and good tune and large enough cam with a good combustion chamber

What motor is this? SBC or LSx or LTx? Whats the planned combination? LS and LT's can run that easilly with E85 but sbc usually dont handle as much compression with same fuel based on the cooling design. It all depends tho on the cam and tune... large cam with lower cranking compression can help life and driveability.

 

it's a gen 1 sbc 355 and the cam is relatively decent sized...