ArticleNucleic acids research2015
Algorithmic co-optimization of genetic constructs and growth conditions: application to 6-ACA, a potential nylon-6 precursor.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 65 citations in OpenAlex.
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- Using design of experiments to guide genetic optimization of engineered metabolic pathways.Journal of industrial microbiology & biotechnology · 2024Review
- Design of Four Small-Molecule-Inducible Systems in the Yeast Chromosome, Applied to Optimize Terpene Biosynthesis.ACS synthetic biology · 2023Article
- Rebooting life: engineering non-natural nucleic acids, proteins and metabolites in microorganisms.Microbial cell factories · 2022Review
- Enzyme-constrained models predict the dynamics of Saccharomyces cerevisiae growth in continuous, batch and fed-batch bioreactors.Microbial biotechnology · 2022Article
- Biosensor-driven, model-based optimization of the orthogonally expressed naringenin biosynthesis pathway.Microbial cell factories · 2022Article
- Advances and trends in microbial production of polyhydroxyalkanoates and their building blocks.Frontiers in bioengineering and biotechnology · 2022Review
- Metabolic Engineering ofACS synthetic biology · 2020Article
- Development of High-Performance Whole Cell Biosensors Aided by Statistical Modeling.ACS synthetic biology · 2020Article
- Evaluation of 244,000 synthetic sequences reveals design principles to optimize translation in Escherichia coli.Nature biotechnology · 2018Article
- Expanding lysine industry: industrial biomanufacturing of lysine and its derivatives.Journal of industrial microbiology & biotechnology · 2018Review
- Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli.Nature communications · 2018Article
- An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals.Communications biology · 2018Article
- Simulation Modeling to Compare High-Throughput, Low-Iteration Optimization Strategies for Metabolic Engineering.Frontiers in microbiology · 2018Article
- Boosting Secondary Metabolite Production and Discovery through the Engineering of Novel Microbial Biosensors.BioMed research international · 2018Review
- Rapid evolution of regulatory element libraries for tunable transcriptional and translational control of gene expression.Synthetic and systems biotechnology · 2017Article
- Engineering Diagnostic and Therapeutic Gut Bacteria.Microbiology spectrum · 2017Review
- Balancing gene expression without library construction via a reusable sRNA pool.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Optimizing bio-production involves strain and process improvements performed as discrete steps. However, environment impacts genotype and a strain that is optimal under one set of conditions may not be under different conditions. We present a methodology to simultaneously vary genetic and process factors, so that both can be guided by design of experiments (DOE). Advances in DNA assembly and gene insulation facilitate this approach by accelerating multi-gene pathway construction and the statistical interpretation of screening data. This is applied to a 6-aminocaproic acid (6-ACA) pathway in Escherichia coli consisting of six heterologous enzymes. A 32-member fraction factorial library is designed that simultaneously perturbs expression and media composition. This is compared to a 64-member full factorial library just varying expression (0.64 Mb of DNA assembly). Statistical analysis of the screening data from these libraries leads to different predictions as to whether the expression of enzymes needs to increase or decrease. Therefore, if genotype and media were varied separately this would lead to a suboptimal combination. This is applied to the design of a strain and media composition that increases 6-ACA from 9 to 48 mg/l in a single optimization step. This work introduces a generalizable platform to co-optimize genetic and non-genetic factors.
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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.