Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (AAA) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the AAA pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The AAA and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the AAA by microbes and plants, and the branching out of AAA metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of AAA must obtain these primary metabolites from their diet. Therefore, the metabolism of AAA by the host animal and the resident microflora are important for the health of all animals. In addition, the AAA metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful AAA-derived compounds produced by gut bacteria are discussed. Apart from the AAA biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with AAA catabolism in plants, AAA degradation via the monoamine and kynurenine pathways in animals, and AAA catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key AAA-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type III CoA-transferase. The past development and current potential for interventions including the development of herbicides and antibiotics that target key enzymes in AAA-related pathways, as well as AAA-linked secondary metabolism leading to antimicrobials are also discussed.

Most studies on amino acids are focused on the proteinogenic amino acids given their essential roles in protein synthesis among other pathways. In addition to 20 ubiquitous amino acids used in protein synthesis, plants synthesize over 250 non-proteinogenic amino acids that are involved in the synthesis of compounds that are anti-herbivory, anti-microbial, response to abiotic stresses, nitrogen storage, toxins against both vertebrates/invertebrates, and plant hormones among others. One such non-proteinogenic acid is β-alanine, which is known mainly for studies on humans. β-Alanine forms a part of pantothenate (vitamin B5), which is incorporated into the universal carbon shuttling compounds Coenzyme A and acyl carrier protein, in all organisms including plants. The focus of this review, however, is on the biosynthesis, metabolism, and the role of β-alanine in plants. There are several functions of β-alanine unique to plants. It is accumulated as a generic stress response molecule involved in protecting plants from temperature extremes, hypoxia, drought, heavy metal shock, and some biotic stresses. There is evidence of its participation in lignin biosynthesis and ethylene production in some species. It is further converted to the osmoprotective compound β-alanine betaine in some species and converted to the antioxidant homoglutathione in others. The polyamines spermine/spermidine, propionate and uracil have been shown to be precursors of β-alanine in plants. However, plants vary in terms of their biosynthetic pathways, and the primary metabolism of β-alanine is far from settled.

Although lysine (Lys) biosynthesis in plants is known to occur by way of a pathway that utilizes diaminopimelic acid (DAP) as a central intermediate, the available evidence suggests that none of the known DAP-pathway variants found in nature occur in plants. A new Lys biosynthesis pathway has been identified in Arabidopsis (Arabidopsis thaliana) that utilizes a novel transaminase that specifically catalyzes the interconversion of tetrahydrodipicolinate and ll-diaminopimelate, a reaction requiring three enzymes in the DAP-pathway variant found in Escherichia coli. The ll-DAP aminotransferase encoded by locus At4g33680 was able to complement the dapD and dapE mutants of E. coli. This result, in conjunction with the kinetic properties and substrate specificity of the enzyme, indicated that ll-DAP aminotransferase functions in the Lys biosynthetic direction under in vivo conditions. Orthologs of At4g33680 were identified in all the cyanobacterial species whose genomes have been sequenced. The Synechocystis sp. ortholog encoded by locus sll0480 showed the same functional properties as At4g33680. These results demonstrate that the Lys biosynthesis pathway in plants and cyanobacteria is distinct from the pathways that have so far been defined in microorganisms.

The synthesis of meso -diaminopimelic acid ( m -DAP) in bacteria is essential for both peptidoglycan and lysine biosynthesis. From genome sequencing data, it was unclear how bacteria of the Chlamydiales order would synthesize m -DAP in the absence of dapD , dapC , and dapE , which are missing from the genome. Here, we assessed the biochemical capacity of Chlamydia trachomatis serovar L2 to synthesize m -DAP. Expression of the chlamydial asd , dapB , and dapF genes in the respective Escherichia coli m -DAP auxotrophic mutants restored the mutants to DAP prototrophy. Screening of a C. trachomatis genomic library in an E. coli Δ dapD DAP auxotroph identified ct390 as encoding an enzyme that restored growth to the Escherichia coli mutant. ct390 also was able to complement an E. coli Δ dapD Δ dapE , but not a Δ dapD Δ dapF mutant, providing genetic evidence that it encodes an aminotransferase that may directly convert tetrahydrodipicolinate to l , l -diaminopimelic acid. This hypothesis was supported by in vitro kinetic analysis of the CT390 protein and the fact that similar properties were demonstrated for the Protochlamydia amoebophila homologue, PC0685. In vivo , the C. trachomatis m -DAP synthesis genes are expressed as early as 8 h after infection. An aminotransferase activity analogous to CT390 recently has been characterized in plants and cyanobacteria. This previously undescribed pathway for m -DAP synthesis supports an evolutionary relationship among the chlamydiae, cyanobacteria, and plants and strengthens the argument that chlamydiae synthesize a cell wall despite the inability of efforts to date to detect peptidoglycan in these organisms.

Pathogenic antibiotic resistant bacteria pose one of the most important health challenges of the 21st century. The overuse and abuse of antibiotics coupled with the natural evolutionary processes of bacteria has led to this crisis. Only incremental advances in antibiotic development have occurred over the last 30 years. Novel classes of molecules, such as engineered antibodies, antibiotic enhancers, siderophore conjugates, engineered phages, photo-switchable antibiotics, and genome editing facilitated by the CRISPR/Cas system, are providing new avenues to facilitate the development of antimicrobial therapies. The informatics revolution is transforming research and development efforts to discover novel antibiotics. The explosion of nanotechnology and micro-engineering is driving the invention of antimicrobial materials, enabling the cultivation of “uncultivable” microbes and creating specific and rapid diagnostic technologies. Finally, a revival in the ecological aspects of microbial disease management, the growth of prebiotics, and integrated management based on the “One Health” model, provide additional avenues to manage this health crisis. These, and future scientific and technological developments, must be coupled and aligned with sound policy and public awareness to address the risks posed by rising antibiotic resistance.

γ-Glutamyl transpeptidases (GGTs) are essential for hydrolysis of the tripeptide glutathione (γ-glutamate-cysteine-glycine) and glutathione S-conjugates since they are the only enzymes known to cleave the amide bond linking the γ-carboxylate of glutamate to cysteine. In Arabidopsis thaliana, four GGT genes have been identified based on homology with animal GGTs. They are designated GGT1 (At4g39640), GGT2 (At4g39650), GGT3 (At1g69820), and GGT4 (At4g29210). By analyzing the expression of each GGT in plants containing GGT:β-glucuronidase fusions, the temporal and spatial pattern of degradation of glutathione and its metabolites was established, revealing appreciable overlap among GGTs. GGT2 exhibited narrow temporal and spatial expression primarily in immature trichomes, developing seeds, and pollen. GGT1 and GGT3 were coexpressed in most organs/tissues. Their expression was highest at sites of rapid growth including the rosette apex, floral stem apex, and seeds and might pinpoint locations where glutathione is delivered to sink tissues to supplement high demand for cysteine. In mature tissues, they were expressed only in vascular tissue. Knockout mutants of GGT2 and GGT4 showed no phenotype. The rosettes of GGT1 knockouts showed premature senescence after flowering. Knockouts of GGT3 showed reduced number of siliques and reduced seed yield. Knockouts were used to localize and assign catalytic activity to each GGT. In the standard GGT assay with γ-glutamyl p-nitroanilide as substrate, GGT1 accounted for 80% to 99% of the activity in all tissues except seeds where GGT2 was 50% of the activity. Protoplasting experiments indicated that both GGT1 and GGT2 are localized extracellularly but have different physical or chemical associations.