I failed to properly consider the 4th carbon problem. So you are right, between the steric problems I mentioned with Roger and the stabilisation of the intermediate it is VERY hard to do with enzymes. I can think of a few routes that may be possible but they all have problems. Besides the CDC approach another good candidate might be oxydation of a CH or COH to a temporary carbocation with subsequent addition of a nucleophilic substrate. Generating and stabilizing the carbocation will of course be very hard.
I failed to properly consider the 4th carbon problem. So you are right, between the steric problems I mentioned with Roger and the stabilisation of the intermediate it is VERY hard to do with enzymes. I can think of a few routes that may be possible but they all have problems. Besides the CDC approach another good candidate might be oxydation of a CH or COH to a temporary carbocation with subsequent addition of a nucleophilic substrate. Generating and stabilizing the carbocation will of course be very hard.