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The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
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Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System
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A generalized platform for artificial intelligence-powered autonomous enzyme engineering.

Nilmani Singh1,2, Stephan Lane1,2,3, Tianhao Yu1,3,4

  • 1Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.

Nature Communications
|July 2, 2025
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Summary
This summary is machine-generated.

Autonomous enzyme engineering platforms accelerate protein design using AI. This new system integrates machine learning and automation, reducing the need for human expertise and enabling rapid advancements in biotechnology and sustainable chemistry.

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Area of Science:

  • Biotechnology
  • Protein Engineering
  • Artificial Intelligence in Science

Background:

  • Proteins are vital molecular machines with broad applications in energy, health, and sustainability.
  • Current protein engineering methods are often slow, costly, and require specialized knowledge.
  • Developing novel proteins with specific functions for practical applications is a significant challenge.

Purpose of the Study:

  • To develop a generally applicable platform for autonomous enzyme engineering.
  • To eliminate the need for human intervention, judgment, and domain expertise in protein engineering.
  • To demonstrate the platform's capability in engineering diverse proteins with enhanced functions.

Main Methods:

  • Integration of machine learning (ML) and large language models (LLMs) with biofoundry automation.
  • A system requiring only an input protein sequence and a quantifiable fitness measure.
  • Autonomous experimental cycles for iterative protein improvement.

Main Results:

  • Engineered Arabidopsis thaliana halide methyltransferase (AtHMT) with a 90-fold increase in substrate preference and a 16-fold increase in ethyltransferase activity.
  • Developed a Yersinia mollaretii phytase (YmPhytase) variant with a 26-fold improvement in activity at neutral pH.
  • Achieved these results in four rounds over four weeks, characterizing fewer than 500 variants per enzyme.

Conclusions:

  • The autonomous enzyme engineering platform significantly accelerates the development of functional proteins.
  • This technology democratizes protein engineering, making it accessible beyond specialist domains.
  • The platform holds potential for rapid advancements in medicine, biotechnology, renewable energy, and sustainable chemistry.