Maybe the problem is more with synthesizing sugar without biological help. After some cursory googling, it sounds like many artificial sweeteners are several orders of magnitude "sweeter" than table sugar, so you'd have to synthesize far more L-sucrose to get a similar effect.

True, you'd need tablespoons of it. :-/

It seems with all the bacteria out there it seems like there would be one that does something obnoxious with L-sucrose.

Fructose is about 50% sweeter than sugar (sucrose), so you can save calories by substituting 2/3 of the quantity of sucrose with fructose

Fructose is metabolised differently IIRC and carries greater risks if anything, possibly this is why HFCS is worse for you.

HFCS isn't particularly high in fructose. Sucrose is essentially 1:1 fructose to glucose. HFCS is typically either 42% or 55% fructose, the rest glucose, so basically the same. Honey and agave nectar are also similar.

I can't say I'm an expert, but I haven't seen anything where consuming fructose is worse overall than other sugars. Fruits for example also tend to be high in fructose, and if you're going to have sugars they tend to be one of the best ways.