ArticleNature chemical biology2021
Peroxisome compartmentalization of a toxic enzyme improves alkaloid production.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 134 citations in OpenAlex.
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- Structural basis of receptor retro-translocation in peroxisomal protein import.bioRxiv : the preprint server for biology · 2026Article
- Benzylisoquinoline Alkaloid Production in Yeast via Norlaudanosoline Improves Titer, Selectivity, and Yield.ACS synthetic biology · 2026Article
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- Functional targeting of membrane transporters and enzymes to peroxisomes.Nature chemical biology · 2025Article
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- Metabolic reprogramming and computation-aided protein engineering for high-level de novo biosynthesis for 2-phenylethanol inSynthetic and systems biotechnology · 2025Article
- De novo biosynthesis of taxifolin in yeast peroxisomes.Microbial cell factories · 2025Article
- ML-enhanced peroxisome capacity enables compartmentalization of multienzyme pathway.Nature chemical biology · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Harnessing organelle engineering to facilitate biofuels and biochemicals production in yeast.Journal of microbiology (Seoul, Korea) · 2025Review
- Engineering microorganisms for enhanced tolerance to toxic end-products and intermediates.FEMS microbiology reviews · 2025Review
- Hierarchical metabolic engineering for rewiring cellular metabolism.FEMS microbiology reviews · 2025Review
- De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.Nature communications · 2024Article
- De novo engineering of programmable and multi-functional biomolecular condensates for controlled biosynthesis.Nature communications · 2024Article
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5 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic cells compartmentalize metabolic pathways in organelles to achieve optimal reaction conditions and avoid crosstalk with cytosolic factors. We found that cytosolic expression of norcoclaurine synthase (NCS), the enzyme that catalyzes the first committed reaction in benzylisoquinoline alkaloid biosynthesis, is toxic in Saccharomyces cerevisiae and, consequently, restricts (S)-reticuline production. We developed a compartmentalization strategy that alleviates NCS toxicity while promoting increased (S)-reticuline titer. This strategy is achieved through efficient targeting of toxic NCS to the peroxisome while, crucially, taking advantage of the free flow of metabolite substrates and products across the peroxisome membrane. We demonstrate that expression of engineered transcription factors can mimic the oleate response for larger peroxisomes, further increasing benzylisoquinoline alkaloid titer without the requirement for peroxisome induction with fatty acids. This work specifically addresses the challenges associated with toxic NCS expression and, more broadly, highlights the potential for engineering organelles with desired characteristics for metabolic engineering.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.