[curiouscat]

A bunch of natural product biosynthesis papers I've been reading seem to start from farnesyl diphosphate as a feed-stock.

Is farnesyl diphosphate a commercially produced / traded product currently? If so, does anyone know what's the dominant route(s?) to farnesyl diphosphate; synthetic or biological.

I know about the mevalonate pathway but that seems more like how nature does it and not sure if that's a commerically viable route.

[discodermolide]

As I'm sure you know this is a starting point for squalene synthesis and hence lanosterol and ultimately cholesterol and a host of other steroids and terpenes. Interestingly there is a pathway to an artemisinin precursor.
See Biosynthesis of Squalene from Farnesyl Diphosphate in Bacteria: Three Steps Catalyzed by Three Enzymes, ACS Sent Sci, 2015, 1(2), 77–82. http://doi.org/10.1021/acscentsci.5b00115.
Also interesting is Jürjens, G., Kirschning, A., & Candito, D. A. (2015). Lessons from the synthetic chemist nature. Natural Product Reports, 32(5), 723–737. http://doi.org/10.1039/c4np00160e.

You can buy it http://www.sigmaaldrich.com/catalog/product/sigma/f6892?lang=en&region=GB but w
expensive.
I guess you can get it by gene manipulated e-coli, although don't quote me on that one. Here is some more info http://www.uniprot.org/uniprot/P14324 .
I would guess its probably easy to synthesise.

[Enthalpy]

The US patent 7,399,323 B2 (2008) gives a path to farnesane that goes through farnesyl diphosphate using microorganisms, possibly bioengineered.

The US patent 7,589,243 B1 (2009, also Amyris biotechnologies) describes compositions of jet fuels based on farnesane, limonane and a few more, to fly with biofuel.

The company claims to have produced kg quantity as an achievement, so the compound wasn't very abundent then. I haven't heard since then about planes flying on farnesane, so supposedly the costs didn't meet the needs.

Pity, because with a melting point around -100°C and a flash point by +109°C, the alkane would also be nice to burn with oxygen in a - you know.

If you manage to produce farnesane and phytane (free of pristane) at a reasonable price, they have more potential uses less sensitive to the last cent, like aeroplane hydraulic fuels, cooling liquids for computers, vacuum lubricants, transformer oil and more
http://www.chemicalforums.com/index.php?topic=56069.msg246917#msg246917
maybe the oligomerization of isoprene fits big amounts better?

[curiouscat]

Thanks @disco & @Enthalpy!

After reading more it seems there's two general options:

(a) I choose a host cell that already has a native pathway to go to FPP from its regular feed

OR

(b) Along with adding the gene for FPP  Bio-product of interest one must also add a Substrate  FPP gene.

So basically, looks like everyone that uses a bio-synthetic pathway that needs FPP synthesizes it in situ.

As an aside, would expecting a cost competitive entirely chemical synthetic path to FPP be reasonable to even think about? Where would you start from?

Looking at the molecule itself it doesn't look super complicated on the scale of what you synthetic organic chemists attempt these days, does it? Not even a ring in there. 

[curiouscat]

If you manage to produce farnesane and phytane (free of pristane) at a reasonable price, they have more potential uses less sensitive to the last cent, like aeroplane hydraulic fuels, cooling liquids for computers, vacuum lubricants, transformer oil and more

In this context, what's a "reasonable" price?

e.g. All the farnesane biotechnology routes I've read of need bioreactors & not simply a solar pond etc. The molecules I was investigating sell at ~$200 /kg.

Doesn't sound anywhere close to what I'd want for a fuel. Even a rocket fuel.

Maybe that's why Amyris has been slowly shifting its PR from biofuels to fine chemicals?

[Enthalpy]

As a vacuum lubricant, I believe you can sell phytane for 50$/100g because alkanes tend to be good lubricants while silicones behave badly under high shear, that is, they don't lubricate.

So just start your company and begin selling for that use.

When your process improves and costs decrease, sell farnesane and phytane as a hydraulic fluid for aeroplanes. As they stay liquid at -70°C and aren't flammable at >> +55°C, you can sell 100kg for >1000usd. Same kind of price as a computer coolant, though each customer may take a smaller amount.

Shrinking the cost further, sell it as a better transformer oil that lasts longer: no multiple bonds, hard to flame, good at cold. In special uses (Arctic, oil platforms...) sell 1000kg for about 10k$.

As a rocket fuel, it depends. I spent thoughts at it because it's perfect for a Mars lander. This needs 10t a few times, for 1M$ each if this makes the lander more reliable (-100°C have been observed on Mars, and nonflammable is nice too). But replacing "kerosene" on a first stage would be difficult: consider <1M$ for 100t.

Jet fuel comes last, when your process runs perfectly in wagon amounts, and I doubt about that. Sell 100t for 100k$.

So yes, I was surprised too that Amyris targeted jet fuel as their first use, and understand too that they changed their mind. A tiny company may be able to live from vacuum lubricant, a less small one from hydraulic fluids and transformer oil.

----------

Synthesis: a strict alkane is more difficult. As a rocket fuel, a nitrogen at each node eases the production
http://www.chemicalforums.com/index.php?topic=56069.msg254340#msg254340

Farnesane has a very abnormal freezing point (and phytane even more so). After many comparisons, this seems to need branches every fourth carbon error-free (or every second one, as 2,4,6-trimethyl-dodecane and tridecane are excellent too). Many isomers and an asymmetric molecule are said to count too, so that CC and CCC as head and tail may improve over C and CC. The regular assembly is exactly what biology does through the pyrophosphate route.

The oligomerization of isoprene was studied in the 70's.
http://www.chemicalforums.com/index.php?topic=56069.msg203815#msg203815
If you access the papers, maybe they have a good catalyst to achieve head-to-tail assembly of isoprene. Anything else would be bad.

A different approach: natural rubber has already the desired patterns, only too long, and possibly with too few isomers. If you can cut the chain precisely, you win. Beware pristane, with one carbon less than phytane, is unhealthy.

The dirt-cheap myrcene is easily hydrogenated to 2,6-dimethyloctane whose dimer is phytane (do you really need farnesane?)... but how? Brominate one terminal carbon, separate the two useful monobromos from the rest, then make a Grignard reagent from one, react with the other? Very obscure to me.

[Enthalpy]

A sketch of the transformation of myrcene to phytane is there
http://www.chemicalforums.com/index.php?topic=56069.msg297534#msg297534
but I suppose it's flawed, or at least in need of improvements.
Obviously, a catalyzed dimerization would be better than the Grignard path.

[Enthalpy]

Yamamoto reports obtaining farnesene from prenyl halide.
http://www.chemicalforums.com/index.php?topic=56069.msg297847#msg297847