ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Pathway Evolution Through a Bottlenecking-Debottlenecking Strategy and Machine Learning-Aided Flux Balancing.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Biosynthesis and Microbial Production of Carminic Acid: From Pathway Elucidation to Synthetic Biology.Microorganisms · 2026Review
- Reimagining Lignin Valorization: Synthetic Biology-Enabled Sustainable Aromatic Carbon Biomanufacturing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metabolic Engineering of Microbial Strains for 1,2,4-Butanetriol Production: Progress and Future Perspectives.Advances in biochemical engineering/biotechnology · 2026Review
- Advances in adaptive laboratory evolution applications forSynthetic and systems biotechnology · 2025Review
- Multiscale metabolic engineering in biological lignin valorization.Innovation (Cambridge (Mass.)) · 2025Review
- Synthetic Biology-Based Engineering Cells for Drug Delivery.Exploration (Beijing, China) · 2025Review
- Application of Cyanobacteria as Chassis Cells in Synthetic Biology.Microorganisms · 2024Review
- Pathway Evolution Through a Bottlenecking-Debottlenecking Strategy and Machine Learning-Aided Flux Balancing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The evolution of pathway enzymes enhances the biosynthesis of high-value chemicals, crucial for pharmaceutical, and agrochemical applications. However, unpredictable evolutionary landscapes of pathway genes often hinder successful evolution. Here, the presence of complex epistasis is identifued within the representative naringenin biosynthetic pathway enzymes, hampering straightforward directed evolution. Subsequently, a biofoundry-assisted strategy is developed for pathway bottlenecking and debottlenecking, enabling the parallel evolution of all pathway enzymes along a predictable evolutionary trajectory in six weeks. This study then utilizes a machine learning model, ProEnsemble, to further balance the pathway by optimizing the transcription of individual genes. The broad applicability of this strategy is demonstrated by constructing an Escherichia coli chassis with evolved and balanced pathway genes, resulting in 3.65 g L
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Registered trials
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.