One in-house ORM I worked with was called TFP, because it was entirely written on a plane ride to Houston, and they named it TFP because the authors liked to say they wouldn't touch it again with a ten foot pole. Their company later thought about trying to sell it, with the name "Technique for Persistence."
Sounds like dependency hell. Gene A only works in the presence of Gene B which only works when there's Gene C which needs Gene A. Knock any one of them out and everything breaks.
Random mutations are like that. It's almost like no-one was planning out how these things should work, and whatever did work stuck.
Weird, huh?
So maybe the environment needs to be changed to support an organism with a smaller genome. The world today is certainly different than when life began. It's probably difficult to evolve the environment, so they'd need to understand what goes wrong with gene deletions and figure out how a different environment could help.
I'm not exactly sure what went wrong, but I think you're really misunderstanding something dnautics said.
M. mycoides certainly does not survive on that. Mycoplasmas need cholesterol and lipids because they lack the HMGCoA reductase pathway and FAS, so all the media you grow them on are enriched for that (started as FBS, but we found horse serum worked great and was cheaper). In general, I think you need a few more things than just that for most basic life (nitrogen, phosphorus, metals)... Is using glucose cheating? Because you could use light for energy and CO2 for carbon, but that adds a ton ton ton of genes...
So this becomes a nitpicky definitional conundrum.
There are no bacteria with smaller genomes today, that was the point of making this one. I was not talking about the global environment either, but the number of options for what substances and concentrations may need to be present in the environment around a cell is certainly very large - making trial and error difficult.
Firstly what constitutes "minimal" depends on what you feed the organism. There's a set of bacteria called phytoplasma which are plant parasites that are missing genes to make nucleotides (even mycoplasmas have those) and they've adapted by sucking nucleotides from their hosts.
Some insider information: Most of the mystery essential genes are vague cell wall proteins. Probably what is going on is that if you knock out too many of these genes, you lose cell wall turgidity and the cell becomes nonviable. So what is important is not so much which of these genes you have, but how many of them you have.
Second insider information, for fun: The "hypothetical minimal genome" (syn2.0 is referred to as HMG in the paper) was actually a backronym because we called it the "hail mary genome" but decided that was inappropriate for publication.