Phenylacetic Acid

Directed Iridium-Catalyzed Hydrogen Isotope Exchange Reactions of Phenylacetic Acid Esters and Amides.[Pubmed:30932249]

Chemistry. 2019 Apr 1.

For the first time, a catalytic protocol for highly selective hydrogen isotope exchange (HIE) of Phenylacetic Acid esters and amides under very mild reaction conditions is reported. Using a homogeneous iridium catalyst supported by a bidentate phosphine-imidazolin-2-imine P,N ligand, the HIE reaction on a series of Phenylacetic Acid derivatives proceeds with high yields, high selectivity and with deuterium incorporation up to 99%. The method is fully adaptable to the specific requirements of tritium chemistry, and its effectiveness was demonstrated by direct tritium labeling of the fungicide benalaxyl and the drug camylofine. Further insights into the mechanism of the HIE reaction with catalyst 1 have been provided utilizing DFT calculation, NMR-studies and X-ray diffraction analysis.

Shunting Phenylacetic Acid Catabolism for Tropone Biosynthesis.[Pubmed:30861343]

ACS Synth Biol. 2019 Mar 26.

Tropone is a seven-membered ring nonbenzenoid aromatic compound. It is the core structure of tropolonoids, which have various biological activities. In this study, a hybrid tropone biosynthetic pathway was designed by connecting Phenylacetic Acid (PAA) degradation with its biosynthesis and reconstituted in Escherichia coli. To simplify pathway construction and optimization, the use of E. coli endogenous genes was maximized and only three exogenous genes were employed. The entire pathway was divided into four modules: the endogenous shikimate pathway module, the hybrid PAA biosynthetic module, the endogenous PAA catabolic module and the heterogeneous tropone biosynthetic module. Efficiency of the PAA catabolic module was enhanced using PAA consumption rate as the indicator. Then, a single point mutation was introduced to inactivate the ALDH domain of PaaZ and the carbon flow was redirected toward tropone synthesis. Assembly of the full pathway led to de novo tropone production with the best titer of 65.2 +/- 1.4 mg/L in shake flask experiment. This study provides a potential alternative for sustainable production of tropone and its derivatives.

Metabolic Engineering of Escherichia coli for para-Amino-Phenylethanol and para-Amino-Phenylacetic Acid Biosynthesis.[Pubmed:30662895]

Front Bioeng Biotechnol. 2019 Jan 4;6:201.

Aromatic amines are an important class of chemicals which are used as building blocks for the synthesis of polymers and pharmaceuticals. In this study we establish a de novo pathway for the biosynthesis of the aromatic amines para-amino-phenylethanol (PAPE) and para-amino-Phenylacetic Acid (4-APA) in Escherichia coli. We combined a synthetic para-amino-l-phenylalanine pathway with the fungal Ehrlich pathway. Therefore, we overexpressed the heterologous genes encoding 4-amino-4-deoxychorismate synthase (pabAB from Corynebacterium glutamicum), 4-amino-4-deoxychorismate mutase and 4-amino-4-deoxyprephenate dehydrogenase (papB and papC from Streptomyces venezuelae) and ThDP-dependent keto-acid decarboxylase (aro10 from Saccharomyces cerevisiae) in E. coli. The resulting para-amino-phenylacetaldehyde either was reduced to PAPE or oxidized to 4-APA. The wild type strain E. coli LJ110 with a plasmid carrying these four genes produced (in shake flask cultures) 11 +/- 1.5 mg l(-1) of PAPE from glucose (4.5 g l(-1)). By the additional cloning and expression of feaB (phenylacetaldehyde dehydrogenase from E. coli) 36 +/- 5 mg l(-1) of 4-APA were obtained from 4.5 g l(-1) glucose. Competing reactions, such as the genes for aminotransferases (aspC and tyrB) or for biosynthesis of L-phenylalanine and L-tyrosine (pheA, tyrA) and for the regulator TyrR were removed. Additionally, the E. coli genes aroFBL were cloned and expressed from a second plasmid. The best producer strains of E. coli showed improved formation of PAPE and 4-APA, respectively. Plasmid-borne expression of an aldehyde reductase (yahK from E. coli) gave best values for PAPE production, whereas feaB-overexpression led to best values for 4-APA. In fed-batch cultivation, the best producer strains achieved 2.5 +/- 0.15 g l(-1) of PAPE from glucose (11% C mol mol-1 glucose) and 3.4 +/- 0.3 g l(-1) of 4-APA (17% C mol mol(-1) glucose), respectively which are the highest values for recombinant strains reported so far.

An Historical Review of Phenylacetic Acid.[Pubmed:30649529]

Plant Cell Physiol. 2019 Jan 15. pii: 5289543.

Plant hormone biology is an ever-evolving field and as such, novel avenues of research must always be sought. Technological and theoretical advancement can also allow for previously dismissed research to yield equally interesting insights into processes now that they are better understood. The auxin PAA is an excellent example of this. PAA is a plant auxin that also possesses substantial anti-microbial activity. It has a broad distribution and has been studied in bacteria, fungi, algae and land plants. Research on this compound in plants was prominent in the 1980s, where its bioactivity and broad distribution were frequently examined. Unfortunately, due to the strong interest in the quintessential auxin, IAA, research on PAA quickly petered out. Recently, several groups have resumed investigations on this hormone in plants, yet, little is known about PAA biology and its physiological role is unclear. PAA biosynthesis from the amino acid Phe invites direct comparisons with previously studied IAA biosynthesis pathways, and recent work has shown that PAA metabolism and signaling appears to be similar to that of IAA. However, given the large gap between previous work and recent investigations, a historical review of this auxin is required to renew our understanding of PAA. Here, previous work on PAA is reassessed in light of recent research in plants and serves as a synthesis of current knowledge on PAA biology.

Cell-Based Biosensor with Dual Signal Outputs for Simultaneous Quantification of Phenylacetic Acid and Phenylethylamine.[Pubmed:30418753]

ACS Synth Biol. 2018 Nov 15.

Despite the importance of 2-Phenylacetic Acid, a plant hormone in the endogenous auxin family, its biosynthesis pathway has yet to be elucidated. In this study, we developed a novel whole-cell biosensor for the simultaneous quantification of 2-Phenylacetic Acid (PA) and 2-phenylethylamine (PEA) through the regulation of bacterial catabolism of aromatic compounds. We used the PA regulon to enable the recognition of PA and PEA. Differentiation of PEA from PA involves the incorporation of the FeaR regulon within the same whole-cell biosensor to report the presence of aromatic amines. The proposed system is highly sensitive to PA as well as PEA.