Metabolic engineering of Escherichia coli for squalene overproduction
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
ABSTRACT Squalene, a lipophilic triterpene with multifaceted bioactivities, faces bioproduction bottlenecks in microbial hosts due to inefficient biosynthetic pathways and limited storage capacity. Here, we address these challenges through systems metabolic engineering integrating redox-balanced 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) variants and membrane lipid remodeling. By developing a hybrid HMGRs system combining NADPH-dependent and NADH-preferred enzymes, squalene production reached 852.06 ± 28.95 mg/L with balanced cofactor utilization. Subsequent engineering of membrane morphology and lipid metabolism generated lipid-enriched elongated cells, through the overexpression of dgs , murG and plsC , boosting squalene production to 970.86 ± 55.67 mg/L. Implementation of delayed induction strategies coupled with 10% dodecane overlay as an in situ recovery system achieved a final squalene titer of 1267.01 mg/L in a 3 L bioreactor. Mechanistic studies revealed fatty acid (FA) and phosphatidylethanolamine (PE) as key reservoirs for squalene in E . coli , with dgs overexpression specifically promoting cellular elongation. This article provides comprehensive insights into engineering strategies and mechanistic perspectives, establishing a universal framework for hydrophobic metabolite biomanufacturing in prokaryotic hosts.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it