Enhancer Phenylacetic acid

Certain factors and product precursors are occasionally added to various fermentation media to iacrease product formation rates, the amount of product formed, or the type of product formed. Examples iaclude the addition of cobalt salts ia the vitamin fermentation, and phenylacetic acid and phenoxyacetic acid for the penicillin G (hen ylpenicillin) and penicillin V (phenoxymethylpenicillin) fermentations, respectively. Biotin is often added to the citric acid fermentation to enhance productivity and the addition of P-ionone vastly iacreases beta-carotene fermentation yields. Also, iaducers play an important role ia some enzyme production fermentations, and specific metaboHc inhibitors often block certain enzymatic steps that result in product accumulation. 

On the other hand, the organic acid and polymer (molecular weight varied from 2000 to 90,000) created no observable solubility enhancement. The investigation of phenyl acetic acid as a cosolute, with concentration > 600 mg/1, shows a slight enhancement for the most hydrophobic DDT. The magnitude of the DDT solubility enhancement/unit mass [19, 249] for phenylacetic acid was much smaller than with the DHA or DFA. They found that the solubility enhancement... 

One shortcoming of the benzoic acid system is the extent of coupling between the car-bo l group and certain lone-pair donors. Insertion of a methylene group between the core (benzene ring) and the functional group (COOH moiety) leads to phenylacetic acids and the establishment of scale from the ionization of X-phenylacetic acids. A flexible method of dealing with the variability of the resonance contribution to the overall electronic demand of a reaction is embodied in the Yukawa-Tsuno equation (86). It includes nor-nial d enhanced resonance contributions to an LFER. 

All the transformations carried out with penicillin acylase and employing phenylacetates or -amides as substrates are hampered by the very limited solubility of these esters in aqueous environments. Although the enzyme tolerates considerable amounts of organic cosolvents, generally their application results in at least a partial deactivation of the enzyme. Since penicillin acylase accepts variations in the phenylacetic acid part of its substrates, pyridyl acetic acid esters were employed to enhance the solubihty of the substrates in aqueous solution. In fact, several simple 4-pyridylacetates turned out to be fairly soluble in aqueous media and were attacked at very acceptable rates by the enzyme [ 19 ]. It is interesting to note that the velocity of the enzymatic transformations depends... 

A magnetic field may affect the flow of electron and ion, resulting in perturbation of the mass transport process near the electrode [37]. For example, in the decarboxylation of phenylacetic acid, the presence of a magnetic field increases the yield of aldehyde, presumably because the supply of molecular oxygen from the bulk solution of the electrode surface is enhanced. 

The same authors also measured the pX value of phenylacetic acid substituted by p-N2 and derived a value of 0 as 2.18. The enhanced value compared with Gp possibly reflects the imperfections of phenylacetic acid for the determination of Gp values for +R substitu-... 

The most important modification of the Perkin reaction was developed by Oglialoro using the sodium salt of acetic acid (e.g., phenylacetic acid, phenoxyacetic acid ) in condensation with acetic anhydride and an aldehyde (e.g., benzaldehyde, paraldehyde ). This type of reaction is referred to as the Perkin-Oglialoro reaction,Perkin-Oglialoro condensation, or Oglialoro modification. Other modifications include the use of different bases as the catalysts, (e.g., NaB(OMe)4-LiCl, CaH2, CsOAc, and CsF ), the use of microwave irradiation and cesium acetate or fluoride in combination with a small amount of pyridine as catalyst and the continuous distillation of acetic acid to enhance the conversion rate. ... 

One of the most simple structures, meeting the requirements for growth substance activity, is that of phenylacetic acid (PAA, VI). Its relatively low activity can be enhanced by substitution, both in the benzene nucleus and in the side-chain. As to the first, the most important data have been summarized by Pybus et (cf. Weintraub and Norman ) to which we refer for details about the separate investigations. 

Table 24.8 gives the structural formulae of the natural penicillins, comprising several closely related structures with aliphatic and aromatic substitutions to the common nucleus. The early impure product contained mixtures of these types. For several reasons penicillin G became the preferred type and the crystalline product of commerce. Phenylacetic acid or its derivatives are used as precursors in the fermentation medium to enhance penicillin biosynthesis and suppress the production of the less desirable types. 

Antibiotic from Pencillium spp. and also other fungal spp. Shows activity against gram-positive bacteria. Starting material for production of 6-Aminopenicillanic acid. Used as a 5% soln. in acetate buffer for gravimetric detn. of Fe. Cryst. [a] +282° (EtOH). Production enhanced by adding Phenylacetic acid to fermentation. 

Aromatic n or /values derived from meta and para substituents tend to be identical, but ortho substituents often give outlying values, e.g., when they permit internal hydrogen bonding, lipophilicity is increased. Apart from this, these n and / values are very sensitive to polar environments. For example, n for chlorine substituted in benzene is 0.71, but this becomes (insertion is in all cases, meta) 0.61 in nitrobenzene, 0.68 in phenylacetic acid, 0.83 in benzoic acid (all ionizable substances are corrected for ionization), 0.98 in aniline, and 1.04 in phenol. This difference of 0.43 between extremes is increased to 0.90 when nitro-group replaces chlorine in the same nuclei (Hansch, Leo et aLy 1973). Two highly polar substituents, particularly if both are nucleophilic, show enhanced lipophilicity (often 0.8) if separated by only one carbon atom, and about half this enhancement if separated by two carbons (Leo, Hansch, and Elkins, 1971 Rekker, 1977, pp. 49y 98, 293). 

Treatment involves a low-protein diet (0.5-0.7 g/kg BW/day) with a sufficient supply of calories. Substitution of essential amino acids (in about the same quantity) is required. The administration of benzoate (0.1-0.25 g/kg BW/day), arginine hydrochloride (1 mmol/kg BW/day) or sodium phenylacetate (0.3-0.5 g/ kg BW/day) (phenylbutyrate tends to be more effective) facilitates nitrogen excretion via other metabolic pathways. (168-170) With an enhanced excretion of orotate or other metabolites of pyrimidine synthesis, the administration of allopurinol leads to an increase in the excretion of nitrogen via metabolites from pyrimidine synthesis. Ammonia and urea precursors are eliminated by haemodialysis. In individual cases, liver transplantation is indicated. (I7l)... 

Downard el al. [9] have reported the application of a phenylacetate layer to glassy carbon macroelectrodes. Their study determined dopamine levels in the presence of ascorbic acid. Differential pulse voltammetry of dopamine and ascorbic acid at both modified and unmodified electrodes showed almost a six-fold enhancement of dopamine anodic peaks at the modified electrodes. For ascorbic acid, while the magnitude of its anodic current remained similar at modified electrodes, the peaks were no longer as well-resolved as for unmodified electrodes. 

The data for the phenylacetic and 3-phenylpropanoic acid systems give values of am (calc) very close to 0.62, considered to be the most reliable value for am of CN (Section III.B). However, the values of ap (calc) for the effects of CN in these acids are appreciably greater than 0.67, considered to be the most reliable value for ap of CN (Section III.B). This supports the views of Wepster and colleagues that cross-conjugation between a +R substituent and methylene, as in structure 9, may enhance the electron-attracting effect of... 

---