Design of synthetic promoters for cyanobacteria with generative deep-learning model
Open accessAbstract
Deep generative models, which can approximate complex data distribution from large datasets, are widely used in biological dataset analysis. In particular, they can identify and unravel hidden traits encoded within a complicated nucleotide sequence, allowing us to design genetic parts with accuracy. Here, we provide a deep-learning based generic framework to design and evaluate synthetic promoters for cyanobacteria using generative models, which was in turn validated with cell-free transcription assay. We developed a deep generative model and a predictive model using a variational autoencoder and convolutional neural network, respectively. Using native promoter sequences of the model unicellular cyanobacterium Synechocystis sp. PCC 6803 as a training dataset, we generated 10 000 synthetic promoter sequences and predicted their strengths. By position weight matrix and k-mer analyses, we confirmed that our model captured a valid feature of cyanobacteria promoters from the dataset. Furthermore, critical subregion identification analysis consistently revealed the importance of the -10 box sequence motif in cyanobacteria promoters. Moreover, we validated that the generated promoter sequence can efficiently drive transcription via cell-free transcription assay. This approach, combining in silico and in vitro studies, will provide a foundation for the rapid design and validation of synthetic promoters, especially for non-model organisms.
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Synthetic promoters are especially useful in metabolic engineering contexts where careful adjustment of multiple gene expression levels is necessary for efficient pathway function.
“Synthetic promoters are especially useful in metabolic engineering contexts where careful adjustment of multiple gene expression levels is necessary for efficient pathway function [100,101].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [101]
The Introduction (page unavailable) says fine-tuning gene expression is crucial for engineering and that synthetic promoters can achieve desired transcriptional activity. The Results (page unavailable) show synthetic promoters with varied strengths and discuss promoters used in cyanobacterial metabolic engineering. The paper does not establish the more specific claim that adjusting multiple genes’ expression levels is necessary for efficient pathway function. (LLM, conf=0.84)
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- Authors
- Seo, E., Choi, Y.-N., Shin, Y. R., Kim, D., & Lee, J. W.
- Affiliations
- Pohang University of Science and Technology (KR)
- Ulsan National Institute of Science and Technology (KR)
- Corresponding author
- Lee, Jeong Wook
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-05-29
- Volume
- 51
- Issue
- 13
- Pages
- 7071-7082
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC10359606
- OpenAlex
- W4378640312
- Cited by
- 61
- References
- 63
- Citations by year
- 2026: 24 · 2025: 21 · 2024: 14 · 2023: 2
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- Bio & Medical Technology Development Program of the National Research Foundation
- Ministry of Science & ICT (2021M3A9I4030408, 2022M3A9I5020804, 2021M3A9I4024840)
- C1 Gas Refinery Program
- MSIT (2015M3D3A1A01064926)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- synthetic promoters, cyanobacteria, Synechocystis sp. PCC 6803, deep generative models, variational autoencoder, convolutional neural networks, cell-free transcription, position weight matrices, k-mer analysis, synthetic biology design, non-model organisms
- MeSH terms
- Deep Learning, Promoter Regions, Genetic, Neural Networks, Computer, Synechocystis
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