molecular biology - What is causing my problem with very low yields when isolating a 42kb yeast plasmid?

I've successfully used the Zymoprep kit, but only for smaller plasmids in 2-hybrid experiments. So their cell lysis enzyme/buffer system works well, but I'd guess that your 42kb plasmid is precipitating out with the genomic DNA.

The standard Qiagen midi columns are capable of capturing large constructs. This has worked wonders for me when I was purifying large BACmids from E. coli - and gets the cost down to $10/sample (it does require additional buffer, but that's a minor expense). It might be worth trying the Qiagen yeast DNA protocols for the midi kit and see if you can isolate your large plasmid?