ArticleProceedings of the National Academy of Sciences of the United States of America2020
Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 80 citations in OpenAlex.
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- Benzylisoquinoline Alkaloid Production in Yeast via Norlaudanosoline Improves Titer, Selectivity, and Yield.ACS synthetic biology · 2026Article
- Calcium activation mechanism of a noncanonical aromatic L-amino acid decarboxylase from psilocybin mushroom Psilocybe cubensis.Communications biology · 2026Article
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- Functional characterization of AtAAS as a 5-hydroxytryptophan decarboxylase linking serotonin formation to melatonin metabolism inFrontiers in plant science · 2026Article
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- Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides.Nature communications · 2025Article
- Evolution of plant metabolism: the state-of-the-art.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Functional and Physiological Characterization of Tyrosine Decarboxylases fromInternational journal of molecular sciences · 2024Article
- Structure and evolution of alanine/serine decarboxylases and the engineering of theanine production.eLife · 2024Article
- Active-Site Oxygen Accessibility and Catalytic Loop Dynamics of Plant Aromatic Amino Acid Decarboxylases from Molecular Simulations.Biochemistry · 2024Article
- Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast.Nature communications · 2024Article
- A terpenoids database with the chemical content as a novel agronomic trait.Database : the journal of biological databases and curation · 2024Article
- Genetic regulation of L-tryptophan metabolism in Psilocybe mexicana supports psilocybin biosynthesis.Fungal biology and biotechnology · 2024Article
- Functional differentiation of olive PLP_deC genes: insights into metabolite biosynthesis and genetic improvement at the whole-genome level.Plant cell reports · 2024Article
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6 authors at 3 institutions in 2 countries.
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Abstract
Radiation of the plant pyridoxal 5'-phosphate (PLP)-dependent aromatic l-amino acid decarboxylase (AAAD) family has yielded an array of paralogous enzymes exhibiting divergent substrate preferences and catalytic mechanisms. Plant AAADs catalyze either the decarboxylation or decarboxylation-dependent oxidative deamination of aromatic l-amino acids to produce aromatic monoamines or aromatic acetaldehydes, respectively. These compounds serve as key precursors for the biosynthesis of several important classes of plant natural products, including indole alkaloids, benzylisoquinoline alkaloids, hydroxycinnamic acid amides, phenylacetaldehyde-derived floral volatiles, and tyrosol derivatives. Here, we present the crystal structures of four functionally distinct plant AAAD paralogs. Through structural and functional analyses, we identify variable structural features of the substrate-binding pocket that underlie the divergent evolution of substrate selectivity toward indole, phenyl, or hydroxyphenyl amino acids in plant AAADs. Moreover, we describe two mechanistic classes of independently arising mutations in AAAD paralogs leading to the convergent evolution of the derived aldehyde synthase activity. Applying knowledge learned from this study, we successfully engineered a shortened benzylisoquinoline alkaloid pathway to produce (S)-norcoclaurine in yeast. This work highlights the pliability of the AAAD fold that allows change of substrate selectivity and access to alternative catalytic mechanisms with only a few mutations.
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