ArticleMetabolic engineering2023
Combinatorial optimization and spatial remodeling of CYPs to control product profile.
Article in Metabolic engineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Metabolic engineering ofaBIOTECH · 2026Article
- Modular reconstruction and multilevel regulation ofSynthetic and systems biotechnology · 2026Article
- Advances in the heterologous biosynthesis of QS saponins: a review.Microbial cell factories · 2026Review
- Engineering Saccharomyces cerevisiae to improve heterologous abscisic acid production.Microbial cell factories · 2026Article
- Cytochrome P450 gene family: cross-pathway functional conservation, novel catalytic reactions, and synthetic biology-driven applications in plant secondary metabolism.Frontiers in plant science · 2026Review
- Enhancing cross-organelle coordination to advance plant cytochrome P450 functionality in yeast.Science advances · 2025Article
- Synthesis of Quillaic Acid through Sustainable C-H Bond Activations.The Journal of organic chemistry · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating inert substrates is a challenge in nature and synthetic chemistry, but essential for creating functionally active molecules. In this work, we used a combinatorial optimization approach to assemble cytochrome P450 monooxygenases (CYPs) and reductases (CPRs) to achieve a target product profile. By creating 110 CYP-CPR pairs and iteratively screening different pairing libraries, we demonstrated a framework for establishing a CYP network that catalyzes six oxidation reactions at three different positions of a chemical scaffold. Target product titer was improved by remodeling endoplasmic reticulum (ER) size and spatially controlling the CYPs' configuration on the ER. Out of 47 potential products that could be synthesized, 86% of the products synthesized by the optimized network was our target compound quillaic acid (QA), the aglycone backbone of many pharmaceutically important saponins, and fermentation achieved QA titer 2.23 g/L.
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Registered trials
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