ArticleNature communications2019
Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 46 citations in OpenAlex.
- Insect-specific aldehyde synthase governs cuticle strength: a selective insecticide target.Science advances · 2026Article
- Genome-scale prediction of gene ontology from mass fingerprints reveals new metabolic gene functions.Life science alliance · 2025Article
- Biotechnological Advances in Sanguinarine and Chelerythrine Production from Plume Poppy (Plants (Basel, Switzerland) · 2025Review
- 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5'-phosphate for cuticle assembly in the mosquito Aedes aegypti.Nature communications · 2025Article
- Molecular basis for the diversification of lincosamide biosynthesis by pyridoxal phosphate-dependent enzymes.Nature chemistry · 2025Article
- Integrated pathway mining and selection of an artificial CYP79-mediated bypass to improve benzylisoquinoline alkaloid biosynthesis.Microbial cell factories · 2024Article
- Mixotrophic culture enhances fucoxanthin production in the haptophyte Pavlova gyrans.Applied microbiology and biotechnology · 2024Article
- Aromatic secondary metabolite production from glycerol was enhanced by amino acid addition in Pichia pastoris.Applied microbiology and biotechnology · 2023Article
- Trace impurities in sodium phosphate influences the physiological activity of Escherichia coli in M9 minimal medium.Scientific reports · 2023Article
- Article
- Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications.Applied microbiology and biotechnology · 2022Review
- Machine learning discovery of missing links that mediate alternative branches to plant alkaloids.Nature communications · 2022Article
- Direct 1,3-butadiene biosynthesis in Escherichia coli via a tailored ferulic acid decarboxylase mutant.Nature communications · 2021Article
- Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route.Chemical science · 2020Article
- Recent Advances in Metabolically Engineered Microorganisms for the Production of Aromatic Chemicals Derived From Aromatic Amino Acids.Frontiers in bioengineering and biotechnology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies have utilized monoamine oxidase (MAO) and L-3,4-dihydroxyphenylalanine decarboxylase (DDC) for microbe-based production of tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) precursor to opioid analgesics. In the current study, a phylogenetically distinct Bombyx mori 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) is identified to bypass MAO and DDC for direct production of 3,4-dihydroxyphenylacetaldehyde (DHPAA) from L-3,4-dihydroxyphenylalanine (L-DOPA). Structure-based enzyme engineering of DHPAAS results in bifunctional switching between aldehyde synthase and decarboxylase activities. Output of dopamine and DHPAA products is fine-tuned by engineered DHPAAS variants with Phe79Tyr, Tyr80Phe and Asn192His catalytic substitutions. Balance of dopamine and DHPAA products enables improved THP biosynthesis via a symmetrical pathway in Escherichia coli. Rationally engineered insect DHPAAS produces (R,S)-THP in a single enzyme system directly from L-DOPA both in vitro and in vivo, at higher yields than that of the wild-type enzyme. However, DHPAAS-mediated downstream BIA production requires further improvement.
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