ArticleNature communications2022
Machine learning discovery of missing links that mediate alternative branches to plant alkaloids.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Benzylisoquinoline Alkaloid Production in Yeast via Norlaudanosoline Improves Titer, Selectivity, and Yield.ACS synthetic biology · 2026Article
- PCA-Based Database Mining Enables the Discovery of Bacterial Carbene Transferases for Stereodivergent Cyclopropanation.Angewandte Chemie (International ed. in English) · 2026Article
- Harnessing synthetic biology for tetraterpenoid astaxanthin production: Recent advances and challenges.Synthetic and systems biotechnology · 2026Review
- Printing technologies for monitoring crop health.Nature communications · 2026Review
- Leveraging artificial intelligence for efficient microbial production.Bioresource technology · 2026Review
- Genome-scale prediction of gene ontology from mass fingerprints reveals new metabolic gene functions.Life science alliance · 2025Article
- From data to discovery: leveraging big data in plant natural products biosynthesis research.The Plant journal : for cell and molecular biology · 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
- Synthetic Biology-Based Engineering Cells for Drug Delivery.Exploration (Beijing, China) · 2025Review
- Microbial Technologies Enhanced by Artificial Intelligence for Healthcare Applications.Microbial biotechnology · 2025Review
- A Guide to Metabolic Network Modeling for Plant Biology.Plants (Basel, Switzerland) · 2025Review
- Integrated metabolomic and transcriptomic analyses ofFrontiers in plant science · 2024Article
- Emerging functions within the enzyme families of plant alkaloid biosynthesis.Phytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2023Article
- Functional annotation of enzyme-encoding genes using deep learning with transformer layers.Nature communications · 2023Article
- Interpol Review of Drug Analysis 2019-2022.Forensic science international. Synergy · 2023Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineering the microbial production of secondary metabolites is limited by the known reactions of correctly annotated enzymes. Therefore, the machine learning discovery of specialized enzymes offers great potential to expand the range of biosynthesis pathways. Benzylisoquinoline alkaloid production is a model example of metabolic engineering with potential to revolutionize the paradigm of sustainable biomanufacturing. Existing bacterial studies utilize a norlaudanosoline pathway, whereas plants contain a more stable norcoclaurine pathway, which is exploited in yeast. However, committed aromatic precursors are still produced using microbial enzymes that remain elusive in plants, and additional downstream missing links remain hidden within highly duplicated plant gene families. In the current study, machine learning is applied to predict and select plant missing link enzymes from homologous candidate sequences. Metabolomics-based characterization of the selected sequences reveals potential aromatic acetaldehyde synthases and phenylpyruvate decarboxylases in reconstructed plant gene-only benzylisoquinoline alkaloid pathways from tyrosine. Synergistic application of the aryl acetaldehyde producing enzymes results in enhanced benzylisoquinoline alkaloid production through hybrid norcoclaurine and norlaudanosoline pathways.
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