Cited by 62Microbial Metabolic Engineering and BioproductionGenomics and Chromatin DynamicsBacterial Genetics and Biotechnology

Design of synthetic promoters for cyanobacteria with generative deep-learning model

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Seo, Euijin, Choi, Yun-Nam, Shin, Ye Rim, Kim, Donghyuk, Lee, Jeong Wook·2023·Nucleic Acids Research

Abstract

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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Research works printed but not linked: 1

  1. [12]Qian Y., Zhang Y., Guo B., Ye S., Wu Y., Zhang J. 2018 IEEE 42nd Annual Computer Software and Applications Conference (COMPSAC). 2018; IEEE 471– 476.

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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
Published
2023-05-29
Volume
51
Issue
13
Pages
7071-7082
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
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
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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