ArticleNature communications2022
Removal of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica.
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 83 papers.
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83 citing papers in PubMed, 231 citations in OpenAlex.
- Shikimate crosstalk enables record-level homogentisic acid production inSynthetic and systems biotechnology · 2026Article
- Metabolic unlocking of lycopene accumulation in the oleaginous yeast Rhodotorula toruloides.Biotechnology letters · 2026Article
- A CRISPR-Cas9 Toolkit Enabling Tunable Integration and Transient Homologous Recombination Enhancement in Yarrowia lipolytica.Biotechnology and bioengineering · 2026Article
- Coupling Carbon-Source Transport with Antioxidant Biosynthesis in Yeast: Product Diversity and Engineering Strategies.Biology · 2026Review
- Contrasting the dynamic changes of carotenoid accumulation in Rhodotorula mucilaginosa under Pb and Cd stress.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Characterisation of metabolic burden in Pseudomonas putida reveals precursor limitation in heterologous lycopene production.Microbial cell factories · 2026Article
- Yeast species resource exploration and application in cell factories.Synthetic and systems biotechnology · 2026Review
- A decoupled transcription platform enables tunable and predictable gene expression in yeast.Nature communications · 2026Article
- Evolutionary tuning of a biosynthetic gene cluster drives furanocoumarin accumulation and diversification.Nature communications · 2026Article
- Truncation ofSynthetic and systems biotechnology · 2026Article
- Efficient vitamin A production in Lipomyces starkeyi through metabolic engineering of the β-carotene and retinoid pathways.Microbial cell factories · 2026Article
- rDNA-mediated multicopy integration and gene dosage quantification system for microbial zeaxanthin biosynthesis.World journal of microbiology & biotechnology · 2026Article
- Engineering Modification for the Efficient Synthesis of β-ionone by Yarrowia lipolytica.Biotechnology journal · 2026Article
- Metabolic Engineering ofJournal of fungi (Basel, Switzerland) · 2026Article
- Strategies for Metabolic Engineering ofMolecules (Basel, Switzerland) · 2026Review
- New perspectives on lycopene: alleviation of sulfamethoxazole-induced inflammation, ER stress, and autophagy in the gills of grass carp.Fish physiology and biochemistry · 2026Article
- CRISPR/Cas9-Mediated Metabolic Engineering of EndophyticACS omega · 2026Article
- Engineering de novo formatotrophy in the non-model yeastNature synthesis · 2026Article
- Enhanced methanol tolerance and utilization in Pichia pastoris revealed by adaptive laboratory evolution.Journal of biological engineering · 2025Article
- Protein design drives synthetic biology research of plant natural products.Biodesign research · 2025Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substrate inhibition of enzymes can be a major obstacle to the production of valuable chemicals in engineered microorganisms. Here, we show substrate inhibition of lycopene cyclase as the main limitation in carotenoid biosynthesis in Yarrowia lipolytica. To overcome this bottleneck, we exploit two independent approaches. Structure-guided protein engineering yields a variant, Y27R, characterized by complete loss of substrate inhibition without reduction of enzymatic activity. Alternatively, establishing a geranylgeranyl pyrophosphate synthase-mediated flux flow restrictor also prevents the onset of substrate inhibition by diverting metabolic flux away from the inhibitory metabolite while maintaining sufficient flux towards product formation. Both approaches result in high levels of near-exclusive β-carotene production. Ultimately, we construct strains capable of producing 39.5 g/L β-carotene at a productivity of 0.165 g/L/h in bioreactor fermentations (a 1441-fold improvement over the initial strain). Our findings provide effective approaches for removing substrate inhibition in engineering pathways for efficient synthesis of natural products.
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