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The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
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High-Temperature Tolerance Protein Engineering through Deep Evolution.

Huanyu Chu1,2, Zhenyang Tian1,2,3, Lingling Hu1,2,4

  • 1Key Laboratory of Engineering Biology for Low-carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, P. R. China.

Biodesign Research
|April 4, 2024
PubMed
Summary
This summary is machine-generated.

We developed DeepEvo, a novel deep learning strategy, to efficiently engineer protein temperature tolerance. This AI-driven approach significantly accelerates the discovery of heat-resistant proteins, overcoming traditional labor-intensive methods.

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Area of Science:

  • Computational Biology
  • Protein Engineering
  • Artificial Intelligence

Background:

  • Traditional protein engineering for enhanced temperature tolerance is labor-intensive, relying on iterative mutagenesis and high-throughput screening.
  • Developing proteins with improved thermal stability is crucial for various biotechnological applications.

Purpose of the Study:

  • To develop an efficient, AI-driven strategy for engineering protein high-temperature tolerance.
  • To reduce the labor and time associated with discovering temperature-resilient proteins.

Main Methods:

  • Developed a deep evolution (DeepEvo) strategy integrating deep learning models for protein sequence generation and selection.
  • Utilized a protein language model as a selector to apply evolutionary pressure in latent sequence spaces.
  • Employed a generative adversarial network (GAN) as a variant generator to create functional protein sequences.

Main Results:

  • Successfully engineered high-temperature tolerance in the model protein glyceraldehyde 3-phosphate dehydrogenase.
  • Obtained 8 high-temperature tolerant variants from only 30 generated sequences.
  • Achieved a remarkable success rate exceeding 26% in identifying functional variants.

Conclusions:

  • The DeepEvo strategy demonstrates high efficiency in engineering protein high-temperature tolerance.
  • Deep learning models can effectively guide protein engineering, accelerating the discovery of proteins with desired functional traits.