ArticleProceedings of the National Academy of Sciences of the United States of America2019
Structure-guided function discovery of an NRPS-like glycine betaine reductase for choline biosynthesis in fungi.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- A Complete Genome Resource and Bio-Control Activity of Soil-Isolated Pseudomonas citronellolis Strain M03 Against Onion-Pathogenic Burkholderia Species.MicrobiologyOpen · 2026Article
- Tryptophanol enhances nitrogen assimilation in marine diatoms.Nature communications · 2026Article
- Discovery of a fungal Tc toxin complex and functional mycoserpin through a novel two-by-two comparative genomics approach.Frontiers in cellular and infection microbiology · 2026Article
- Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors.Nature chemical biology · 2025Article
- Oral intake of deuterated choline at clinical dose for metabolic imaging of brain tumors.Npj imaging · 2025Article
- Genome Analysis ofJournal of fungi (Basel, Switzerland) · 2025Article
- Comparative genomics reveals substantial divergence in metal sensitive and metal tolerant isolates of the ericoid mycorrhizal fungus Oidiodendron maius.Mycorrhiza · 2025Article
- Animal-Encoded Nonribosomal Pathway to Bursatellin Analogs.Journal of the American Chemical Society · 2025Article
- The encoded and expressed biosynthetic potential of Greenland Ice Sheet microbes.Frontiers in microbiology · 2025Article
- Ectopic expression of choline oxidase (3 Biotech · 2024Article
- Genomic Sequencing and Functional Analysis of the Ex-Type Strain ofJournal of fungi (Basel, Switzerland) · 2024Article
- NRPS-like ATRR in Plant-Parasitic Nematodes Involved in Glycine Betaine Metabolism to Promote Parasitism.International journal of molecular sciences · 2024Article
- Genomic insights into the evolution and adaptation of secondary metabolite gene clusters in fungicolous species Cladobotryum mycophilum ATHUM6906.G3 (Bethesda, Md.) · 2024Article
- Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases.Natural product reports · 2023Review
- Enzymatic reactions towards aldehydes: An overview.Flavour and fragrance journal · 2023Review
- Characterization and catalytic investigation of fungal single-module nonribosomal peptide synthetase in terpene-amino acid meroterpenoid biosynthesis.Journal of industrial microbiology & biotechnology · 2023Article
- Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining.Natural product reports · 2023Review
- Genomic and Metabolomic Analyses of the Medicinal FungusJournal of fungi (Basel, Switzerland) · 2022Article
- Glycine betaine uptake and metabolism in marine microbial communities.Environmental microbiology · 2022Article
- Enzymatic Synthesis of Diverse Heterocycles by a Noncanonical Nonribosomal Peptide Synthetase.ACS chemical biology · 2021Article
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3 authors at 1 institution in 1 country.
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Abstract
Nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes have diverse functions in primary and secondary metabolisms. By using a structure-guided approach, we uncovered the function of a NRPS-like enzyme with unusual domain architecture, catalyzing two sequential two-electron reductions of glycine betaine to choline. Structural analysis based on the homology model suggests cation-π interactions as the major substrate specificity determinant, which was verified using substrate analogs and inhibitors. Bioinformatic analysis indicates this NRPS-like glycine betaine reductase is highly conserved and widespread in kingdom fungi. Genetic knockout experiments confirmed its role in choline biosynthesis and maintaining glycine betaine homeostasis in fungi. Our findings demonstrate that the oxidative choline-glycine betaine degradation pathway can operate in a fully reversible fashion and provide insight in understanding fungal choline metabolism. The use of an NRPS-like enzyme for reductive choline formation is energetically efficient compared with known pathways. Our discovery also underscores the capabilities of the structure-guided approach in assigning functions of uncharacterized multidomain proteins, which can potentially aid functional discovery of new enzymes by genome mining.
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