A multipoint mutation is analogous to Systems must take performance hits to get out of local optima - in the tech tree model this means having one or more low impact precursor nodes.
Almost by definition you need multipoint mutations to fix Structural Constraints because structural constraints mean that there are two or more interlocking dependencies.
In biology, it’s (impossible?) to have a precursor with a single mutation that renders it inviable give rise to a precursor that has a second mutation that addresses issues from the first and builds on it. We’ve used genetic engineering and mutation breeding to get around this fact. (What does technological genetic engineering look like? and What does technological mutation breeding look like?)
In technology a non-viable (non impactful) precursor can be kept alive in a lab or in an obscure paper somewhere. These are unexploited Leonardo Ideas! Which may give a hint that the process of finding unexploited Leonardo ideas (Leonardo Ideas can be systematically identified) may be part of the answer to What does technological genetic engineering look like?