Conserved Molecular Mechanism of TyrA Dehydrogenase Substrate Specificity Underlying Alternative Tyrosine Biosynthetic Pathways in Plants and Microbes

Craig A Schenck,Yusen Men,Hiroshi A Maeda

doi:10.3389/fmolb.2017.00073

Craig A Schenck, Yusen Men + Show 1 more

Open Access

https://doi.org/10.3389/fmolb.2017.00073

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Abstract

L-Tyrosine (Tyr) is an aromatic amino acid synthesized de novo in plants and microbes. In animals, Tyr must be obtained through their diet or synthesized from L-phenylalanine. In addition to protein synthesis, Tyr serves as the precursor of neurotransmitters (e.g., dopamine and epinephrine) in animals and of numerous plant natural products, which serve essential functions in both plants and humans (e.g., vitamin E and morphine). Tyr is synthesized via two alternative routes mediated by a TyrA family enzyme, prephenate, or arogenate dehydrogenase (PDH/TyrAp or ADH/TyrAa), typically found in microbes and plants, respectively. Although ADH activity is also found in some bacteria, the origin of arogenate-specific TyrAa enzymes is unknown. We recently identified an acidic Asp222 residue that confers ADH activity in plant TyrAs. In this study, structure-guided phylogenetic analyses identified bacterial homologs, closely-related to plant TyrAs, that also have an acidic 222 residue and ADH activity. A more distant archaeon TyrA that preferred PDH activity had a non-acidic Gln, whose substitution to Glu introduced ADH activity. These results indicate that the conserved molecular mechanism operated during the evolution of arogenate-specific TyrAa in both plants and microbes.

Highlights

L-Tyrosine (Tyr) is an aromatic amino acid required for protein synthesis in all organisms, but synthesized de novo in plants and microbes
Structure-guided phylogenetic analyses from diverse organisms identified ADH-like sequences in some bacteria, e.g., spirochaetes, α- and δ-proteobacteria, which form a monophyletic clade with plant TyrAs (Figure 2, Figure S1)
Biochemical characterization further demonstrated that TyrAs from spirochaetes and α-proteobacteria have ADH, but not PDH activity (Figures 3A,B)

Summary

Introduction

L-Tyrosine (Tyr) is an aromatic amino acid required for protein synthesis in all organisms, but synthesized de novo in plants and microbes. Tyr serves as the precursor to numerous plant natural products with diverse functions such as electron carriers (e.g., plastoquinone and ubiquinone; Millner and Barber, 1984), defense (e.g., dhurrin and rosmarinic acid; Petersen, 2013; Gleadow and Møller, 2014), and pollinator attraction (e.g., betalain pigments; Gandía-Herrero and García-Carmona, 2013). Some of these natural products serve medicinal and nutritional roles in humans such as antioxidants (vitamin E; Falk and Munné-Bosch, 2010), and analgesics (e.g., morphine; Sato et al, 2007). In most microbes prephenate is first converted into 4-hydroxyphenylpyruvate

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