Hi, I'm writing for those who might encounter the same problem as me. Indirect spoilers ahead, but if you encounter this, you'll probably already know about them. Also, I'm still playing this mod on Factorio v1.1.

Some time after fighting a nest of enemies, my game's UPS dropped from 60 to around 5-15. I spent quite a long time trying to figure out what was causing it, and I found out the problem was that a huge number of enemies had been generated. What helped me was removing all enemy units using a console command (don't worry about gameplay, they will still be spawning):

/c game.forces["protomolecule"].kill_all_units()

More technical info for those interested:

After seeing that this fixed the problem, I returned to a previous save to test how many units there were. I used this script (I'm not well-versed in Factorio scripting, so I'm posting this for more competent people to double-check if they wish):

local enemy_force = game.forces["protomolecule"]
local total_enemy_units = 0

for _, entity_prototype in pairs(game.entity_prototypes) do
    if entity_prototype.type == "unit" then
        total_enemy_units = total_enemy_units + enemy_force.get_entity_count(entity_prototype.name)
    end
end

game.player.print("Total enemy units: " .. total_enemy_units)

There were 27,310 units of the protomolecule force (and 36,130 units of the regular enemy force, but as far as I've heard, they are well optimized not to consume much UPS while not in visible chunks).

I built a 900 spm factory before completing the game. UPS went down to as low as 2 whenever artillery agitated the enemies :D

Yeah I ran into that too. The PM mainbase produces a ton of pollution so the spawners go nuts and make a million of them. Thanks for the tip about there being a separate force for them, that helped me get my save file back up and running. I wonder if the biters and PM forces are hostile to each other? I never saw them engage each other or occupy the same territory. I mean given how virulent and heavily-armed the PMs are the bugs probably got clowned on immediately and wiped out before I came by to investigate. That's a shame, it would've been interesting to navigate a battlefield with multiple hostile forces on it. In another mod I spent some time tricking biters into attacking enemy bases while also trying to avoid the base defenses myself. It's an interesting angle.