Hydroxypropionic production

Contaminants and by-products which are usually present in 2- and 4-aminophenol made by catalytic reduction can be reduced or even removed completely by a variety of procedures. These include treatment with 2-propanol (74), with aUphatic, cycloaUphatic, or aromatic ketones (75), with aromatic amines (76), with toluene or low mass alkyl acetates (77), or with phosphoric acid, hydroxyacetic acid, hydroxypropionic acid, or citric acid (78). In addition, purity may be enhanced by extraction with methylene chloride, chloroform (79), or nitrobenzene (80). 

There are two pathways for the degradation of nitriles (a) direct formation of carboxylic acids by the activity of a nitrilase, for example, in Bacillus sp. strain OxB-1 and P. syringae B728a (b) hydration to amides followed by hydrolysis, for example, in P. chlororaphis (Oinuma et al. 2003). The monomer acrylonitrile occurs in wastewater from the production of polyacrylonitrile (PAN), and is hydrolyzed by bacteria to acrylate by the combined activity of a nitrilase (hydratase) and an amidase. Acrylate is then degraded by hydration to either lactate or P-hydroxypropionate. The nitrilase or amidase is also capable of hydrolyzing the nitrile group in a number of other nitriles (Robertson et al. 2004) including PAN (Tauber et al. 2000). 

Microorganisms have also been developed to produce alternative products, such as lactic acid [65], propane-1,3-diol [67], 3-hydroxypropionic acid [68], butane-2,3-diol [69] and numerous other intermediates. For instance, bacteria such as the Clostridium acetobutylicum ferment free sugars to C4 oxygenates such as butyric acid or butanol. They form the C4 oxygenates by Aldol condensation of the acetaldehyde intermediates. The Weizmann process exploits this property to ferment starch feedstock anaerobically at 37 °C to produce a mixture of w-butanol, acetone and ethanol in a volume ratio of 70 25 5 [3],... 

Methylene chloride-soluble residues. Methylene chloride-or chloroform-soluble C-labeled products were major residues in all of the plant tissues examined except peanut cell ciiltures (Figure 3). Chloroform-soluble C accounted for 59.2 of the radioactivity isolated from peanut roots 48 hr after treatment with [ C]PCNB. The radioactivity was in the form of PCNB (28.7 ), pentachloroaniline (22.5 ), pentachlorothiophenol (2.6 ) pentachlorothloanlsole (3.1 ) pentachlorothloanlsole sulfoxide (0.5 ) S-(pentachlorophenyl)-2-thioaoetic acid [(S-(PCP)ThioAcetate] (0.5 ) and S-(pentachlorophenyl)-3-thio-2-hydroxypropionic acid [S-(PCP)ThioLactate] (0.2 ) and S-(PCP)Cys (trace) (J), The structures of these compounds are shown in Figure 13. Based on TLC, the last three compounds in this list were classified as polar chloroform- or methylene chloride-soluble residues and the remaining compounds were classified as nonpolar residues. 

Methanolysis of 0-propiolactone with a trace of hydroxide catalyst gives a good yield of methyl 3 -hydroxypropionic acid, but with an equimolecular quantity of sodium methoxide the product is sodium 3-methoxypropionate (equation 48) (64hc(19-2)729). 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

A cooled mixture of 200 g. (109 cc.) of concentrated sulfuric acid (2 moles) and 300 cc. of water is now added slowly with careful cooling (Note 2), the pasty mixture being stirred with a thermometer and the temperature not being allowed to rise above 35°- Sodium sulfate crystallizes during this addition. The mass is now shaken vigorously with 400 cc. of ether and allowed to stand for some minutes. The ether is then decanted as completely as possible and the residue filtered with suction. The sodium sulfate is now shaken with six successive 300-cc. portions of ether, the ether solutions being subsequently employed for extraction of the filtrate. This latter requires ro-r4 such extractions (each with 300-400 cc. of ether) for the satisfactory extraction of the /3-hydroxypropionic acid. The combined ethereal solution is dried over 50 g. of anhydrous sodium sulfate and the ether distilled from a water bath, the temperature of which is not allowed to rise above 50°. The product is then concentrated under reduced pressure from a water bath maintained at 55-60°. The residue should have attained constant weight after four to six hours of this treatment it consists of a sirupy liquid of pale straw color which contains 75-80 per cent of /3-hydroxypropionic acid (by titration) (Note 3). The yield is 120-225 g. (28-31 per cent of the theoretical amount). 

Hydroxypropionic acid is an uncrystallizable and hygroscopic sirup. The 20-25 Pcr cent °f impurity remaining in the final product is largely water. 

The pathway can be divided into two metabolic cycles (Figure 3.4). In the first cycle, acetyl-CoA is carboxylated to malonyl-CoA, which is subsequently reduced and converted into propionyl-CoA via 3-hydroxypropionate as a free intermediate. Propionyl-CoA is carboxylated to methylmalonyl-CoA, which is subsequently converted to succinyl-CoA the latter is then used to activate L-malate by succinyl-CoA L-malate coenzyme A transferase, which forms L-malyl-CoA and succinate. Succinate is oxidized to L-malate via conventional steps. L-Malyl-CoA, the second characteristic intermediate of this cycle, is cleaved by L-malyl-CoA/P-methylmalyl-CoA lyase, thus regenerating the starting molecule acetyl-CoA and releasing gly-oxylate as a first carbon-fixation product [27]. 

The product of acetyl-CoA carboxylase reaction, malonyl-CoA, is reduced via malonate semialdehyde to 3-hydroxypropionate, which is further reductively converted to propionyl-CoA. Propionyl-CoA is carboxylated to (S)-methylmalonyl-CoA by the same carboxylase. (S)-Methylmalonyl-CoA is isomerized to (R)-methylmal-onyl-CoA, followed by carbon rearrangement to succinyl-CoA by coenzyme B 12-dependent methylmalonyl-CoA mutase. Succinyl-CoA is further reduced to succinate semialdehyde and then to 4-hydroxybutyrate. The latter compound is converted into two acetyl-CoA molecules via 4-hydroxybutyryl-CoA dehydratase, a key enzyme of the pathway. 4-Hydroxybutyryl-CoA dehydratase is a [4Fe-4S] cluster and FAD-containing enzyme that catalyzes the elimination of water from 4-hydroxybutyryl-CoA by a ketyl radical mechanism to yield crotonyl-CoA [34]. Conversion of the latter into two molecules of acetyl-CoA proceeds via normal P-oxidation steps. Hence, the 3-hydroxypropionate/4-hydroxybutyrate cycle (as illustrated in Figure 3.5) can be divided into two parts. In the first part, acetyl-CoA and two bicarbonate molecules are transformed to succinyl-CoA, while in the second part succinyl-CoA is converted to two acetyl-CoA molecules. 

Platform chemicals are compounds that serve as building blocks for numerous chemical intermediates and end products. An example is ethylene, which serves as the feedstock for derivatives such as acetaldehyde, ethylene dichloride, ethylene oxide, polyethylene, vinyl acetate, and ethyl acetate. Biobased chemicals such as succinic acid, 3-hydroxypropionic acid (3-HP), and butanol also have the potential to be converted into multiple derivatives, some of which are commodity chemicals and others that are higher-value chemicals. 

Suthers, P.F. and Cameron, D.C. 2005. Production of 3-Hydroxypropionic Acid in Recombinant Organisms. United States Patent number 6852517. 

Suthers PF, Cameron DC (2001) Production of 3-hydroxypropionic acid in recombinant organisms. PCT WO 01-16346... 

The presence of the /3-hydroxypropionic ester unit in deacetylpicraline is established by oxidation with chromic acid in acetone, which yields an aldehyde base, picralinal, C21H22N2O4 the latter is readily deform yla ted by short treatment with methanolic potassium hydroxide, which affords picrinine in quantitative yield. Reduction of picralinal with sodium borohydride regenerates deacetylpicraline. Vigorous treatment of deacetylpicraline with sodium borohydride gives a noncrystalline indoline base, which exhibits the UV-absorption of an anilinium ion in concentrated perchloric acid hence, the Na-carbinol-amine ether function must have suffered reduction. Since acetylation of the noncrystalline base gives a product which exhibits acylaniline UV-absorption, picraline and its derivatives must contain an NaH group (53, 54). 

Some preliminary studies were conducted to determine whether one of two proposed reactions could account for the appearance of pyruvate from dalapon. The precursor of pyruvate in this system is probably the a-hydroxy-a-chloropropionate. This compound is unstable and will spontaneously give rise to pyruvic acid. The enzyme apparently forms a-chloro-a-hydroxypropionate from dalapon. One reaction system by which the enzyme could form a-chloro-a-hydroxypropionate from dalapon would involve a direct substitution reaction (Reaction 1). In this case there would be a direct nucleophilic attack at carbon-2, led by a hydroxyl group to form the desired product. 

Lactic acid consists of a mixture of 2-hydroxypropionic acid, its condensation products, such as lactoyllactic acid and other polylactic acids, and water. It is usually in the form of the racemate, (] 5)-lactic acid, but in some cases the (S)-(- -)-isomer is predominant. 

Lactic acid (2-hydroxypropionic acid) is a naturally occurring multifunctional organic acid that is found in many food products, particularly in those which involve natural or processed fermented food preparations. Currently, more than 70% of lactic acid is used as acidulents, food preservatives, and feedstock for the manufacture of calcium stearoyl-2-lactylates in the baking industry. The consumption of lactic acid is estimated to be around 30 million lb in the US with an estimated increase of 6% per year. Therefore, lactic acid is an intermediate-volume specialty chemical used chiefly for food processing. 

LA Starting product for PLA is 2-hydroxypropionic acid (lactic acid, LA), which also can be produced bio technologic ally. Basic materials for LA are agricultural raw and waste materials these will be converted by means of a bacterial fermentation process into L-2-hydroxypropionic acid (r-lactic acid, l-LA). 

Formic and acetic acids are most attractive, but would probably be volatile under scrubber conditions (8). Succinic and lactic acids would not be cost-effective if purchased at market price. Fumaric acid is more subject to oxidative degradation. Phthalic and Benzoic acids may give undesirable aromatic degradation products. Therefore, the most useful buffers appear to be hydroxypropionic, sulfosuccinic, fumaric, sulfopropionic, adipic, and hydroxyacetic. 

Waste or byproduct organic acids could be cost-effective alternatives. Adipic acid production by nitric acid oxidation of cyclohexanol/cyclohexanone generates byproduct consisting of glutaric and succinic acids which should perform like adipic acid. Air oxidation of cyclohexane to produce cyclohexanone as an intermediate for caprolactam generates a waste solution of adipic, hydroxyvaleric, glutaric, and other acids. This product should be comparable to a mixture of adipic and hydroxypropionic acids. 

Oxidation of aqueous solutions (10% wlw ) of 3-hydroxypropionaldehyde (HPA) in the presence of 3 % Pd/C catalysts at pH 8 produces malonic acid. Complete conversion, with 96.7 % yield, was achieved with large amounts of catalyst (33% wlw Pd relative to HPA) [91]. Starting from 3-hydroxypropionic acid the malonic acid selectivity was 95.4 % at 97 % conversion. In the presence of 5 % Pt/C catalysts (28 % wlw Pt with respect to HPA), aqueous solutions (10% wlw) of 3-hydroxypropionaldehyde were oxidized into 3-hydroxypropionic acid, an intermediate used to prepare pharmaceutical and agricultural products. The best yield, obtained without pH regulation, was 92.9% at 97.2% conversion [92]. 

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