The PTM situation is a bit worse actually. First, of all the PTMs, high mannose N-glycans can be recapitulated (with the right knockouts). It’s the complex/hybrid that are completely missing.

Second, the O-glycans are completely different to humans. Unless you’re looking at alpha-DG, and a handful of other proteins, you’re going to get the wrong glycosylation. This is a problem for two reasons: a) the alpha-Mannose does completely different things to the protein backbone compared to alpha-GalNAc, or probably alpha-Fucose etc, and b) those yeast PMT enzymes don’t seem to care where they throw sugars on, so they’re going to probably glycosylate something that shouldn’t be glycosylated.

This is to say nothing about the different suite of PC-processing enzymes and zymogen activation in yeast too.

So here’s my free solution to solve this: On all mated cells, do a ConA enrichment and identify where there is O-glycosylation (mass spectrometry). If it’s on your target protein, drop the data?

But otherwise, if you are interested in yeast interaction, looks like a cool technique!