Carbon Management Implications for R&D in the Chemical Sciences and Technology (2001) / Chapter Skim
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12. Chemicals from Plants
12. Chemicals from Plants
Pages 185-208
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From page 185... ...
It has been estimated that 98% of all chemicals produced in the United States in excess of 2 × 107 kg are synthesized from petroleum and natural gas.1 By contrast, chemicals isolated as natural products from plants or produced by microbes from carbohydrate feedstocks are typically restricted to ultrafine chemicals and a relatively few fine chemicals. The goal of our research effort is to ascertain how the widest possible spectrum of commodity, pseudo commodity, fine, and ultrafine chemicals can be synthesized from polyol starting materials such as d-glucose, d-xylose, larabinose, and glycerol.
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From page 186... ...
l-Phenylalanine, l-tyrosine, l-tryptophan, and aromatic vitamins must be added to cultures to enable the microbial construct to grow, but they inhibit DAHP synthase activity and thus the flow of carbon into the common pathway. Employment of aroFFBR and the encoded DAHP synthase that is insensitive to feedback inhibition is thus critical to directing increased carbon flow into aromatic amino acid biosynthesis.6 Individual common pathway enzymes become impediments to increased carbon flow due to their inability to convert substrate into product at a rate sufficiently rapid to avoid cytoplasmic accumulation and subsequent export of the substrate into the culture medium.7 3-Dehydroquinate synthase and shikimate dehydrogenase are both impediments to increased carbon flow that result, respectively, in accumu O O CO2H HO CO2H multiple steps multiple steps HO OH O NH 2 HO OH OH HN OH O shikimic acid GS4104 quinic acid FIGURE 12.1 Starting materials for the synthesis of the neuraminidase inhibtor GS4104.
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From page 187... ...
coli-catalyzed synthesis of shikimic acid from glucose is 86%.8 Achieving such yields would likely move shikimic acid from the realm of a scarce natural product used as a chiral synthon to the realm of an inexpensive building block chemical possessed of disposable chirality and an attractive assemblage of carbon atoms. INTERFACING AND BIOCATALYSIS Although shikimic acid and quinic acid are certainly not large-volume chemicals, these hydroaromatics provide an intriguing entry point into large-volume fine chemicals and pseudocommodity chemi
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From page 188... ...
For example, Woskresensky reported that hydroquinone was produced upon "dry distillation" of quinic acid in 1838.9 The "quin" root of hydroquinone reflects this genesis. Eykmann reported in 1891 that refluxing concentrated HCl solutions of shikimic acid resulted in the formation of p-hydroxybenzoic acid.10 With microbe-catalyzed conversions of glucose into shikimic acid and quinic acid, the opportunity presents itself to synthesize hydroquinone and p-hydroxybenzoic acid from glucose.
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From page 189... ...
The loss of shikimic acid during isolation from fermentation broth, the crude yield for acidcatalyzed dehydration of shikimic acid, and the loss of p-hydroxybenzoic acid during product purification reduce the overall yield of p-hydroxybenzoic acid synthesized from glucose. Indeed, the overall yield for synthesis of p-hydroxybenzoic acid via acid-catalyzed dehydration of shikimic acid is reduced to the point where this route does not have an advantage in yield relative to direct, microbe-catalyzed conversion of glucose into p-hydroxybenzoic acid.
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From page 190... ...
Carbon flow directed into the common pathway of aromatic amino acid biosynthesis can thus not proceed beyond 3-dehydroquinic acid (Figure 12.5)
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From page 191... ...
Metal-catalyzed oxidations have to be compatible with use of water as the reaction solvent. Preferably, elaborated catalysts should be sufficiently robust to mediate the oxidation of quinic acid in clarified, crude fermentor broth.
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From page 192... ...
.23 Catalytic, chemical hydrogenation of the cis,cis-muconic acid then afforded adipic acid (Figure 12.7) .23 Directing increased carbon flow down the common pathway of aromatic amino acid biosynthesis employed the same strategies as previously described for microbe-catalyzed synthesis of shikimic acid.
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From page 193... ...
coli host containing three plasmids was used to catalyze the conversion of glucose into cis,cis-muconic acid under shake flask conditions.23 Our most recent construct uses a single plasmid and catalyzes the conversion of glucose into cis,cis-muconic acid under controlled, fedbatch fermentor conditions similar to those employed for microbe-catalyzed synthesis of shikimic acid and quinic acid from glucose. After removal of the biocatalyst, the clarified fermentation broth is treated with activated carbon to remove unidentified molecules in the broth that poison platinum catalysts.
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From page 194... ...
However, the bioproducts industry is producing an expanding variety of starting materials such as l-lysine and lactic acid at commodity chemical prices and volumes. Transforming this new generation of starting materials into existing and new chemical products requires the development of new syntheses and new synthetic methodologies compatible with use of water and fermentation broths as the reaction solvent.
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From page 195... ...
They "cheat," somewhat and equate acids with their salts. In your process, you mentioned, adipate, not adipic acid.
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From page 196... ...
There is a big difference between a microbe in this context and a transgenic plant that is in the outside world. For the latter, there is more concern about mobilized genetic elements and the issue of food.
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From page 197... ...
When converting a carboxylic acid to the alcohol, the process typically runs at between 100 and 200°C and at 3,000 to 5,000 pounds per square inch hydrogen. So I consider that an example of a very basic organic reaction.
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From page 198... ...
The knowledge didn't exist before. This happened to us in trying to figure out how to remove the residual lactide monomer effectively.
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From page 199... ...
What we are hearing at the same time is that the basic organometallic and process engineering is critical to what is happening or what is needed in the carbon management area. Funding inequity is a very serious problem, or at least a phenomenon.
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From page 200... ...
It is desperately trying to deal with this metabolic engineering issue. Basically, what is going on here is that, Americans are very good at discovering things and then the Japanese eat our lunch.
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From page 201... ...
David Keith, Carnegie Mellon University: This panel has illustrated wonderfully the enormous potential of chemical and biochemical process engineering to really improve the environmental performance of our energy and chemical technologies. I think the promise is extraordinary.
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From page 202... ...
David Keith: I certainly agree we don't need to teach people how to save Bambi. What I want to do is connect hard-headed assessments of the environmental costs of various industrial activities to the folks who are designing those processes.
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From page 203... ...
I have proposed that we run a professional development program at the national level, funded through industry. We should take those teachers who are educated in the biological sciences, and who are being forced to teach physics and chemistry without solid knowledge in it, and run a professional development program in the molecular sciences.
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From page 204... ...
If the cost of carbon goes up, all of the things discussed earlier are important, but let's not forget the biggest driver in it -- which is the combustion of fossil fuels. John Frost: If you look at nature in terms of CO2 removal capability, there are ribulose bisphosphate carboxylase, and phosphoenolpyruvate carboxylase, which are marvelous.
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From page 205... ...
It would absolutely force people to start talking to people in other fields. To give a classic example, a very good transgenic plant person received a very large grant to do functional genomics in hemicellulose biosynthesis.
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From page 206... ...
I think the other way to go is look at the properties that we are after and go after alternates -- polylactic acid, for example, instead of styrene. Instead of building these big massive plants that consume lots of energy and fossil fuels, find some other way to get the desired properties from a different product altogether.
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From page 207... ...
You want facilitated diffusion for glucose uptake so that you are not sacrificing yield for rates of glucose uptake because you can always have plenty of glucose in a tank. You want an organism that works very effectively at low pH.
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From page 208... ...
I have learned a great deal. I have gained a new perspective on how important the carbon management issue it is, how complex it is, how difficult it is to discern green versus non-green, and what the life-cycle analyses are.
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