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Updated: Mar 21, 2026

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
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PHA synthase variant design using a conditional variational autoencoder.

Tuula Tenkanen1, Anna Ylinen1, Paula Jouhten2

  • 1VTT Technical Research Centre of Finland Ltd., Espoo, Finland.

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|March 19, 2026
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Summary
This summary is machine-generated.

Artificial intelligence designed novel polyhydroxyalkanoate (PHA) synthases, expanding enzyme capabilities. Two engineered enzymes were confirmed active, producing poly(hydroxybutyrate) (PHB) in yeast.

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Area of Science:

  • Biochemistry
  • Enzyme Engineering
  • Synthetic Biology

Background:

  • Polyhydroxyalkanoate (PHA) synthases are dimeric enzymes crucial for synthesizing PHAs, biopolymers with diverse properties.
  • Natural PHA synthases exhibit limited specificity, restricting the range of R-hydroxyacids they can polymerize.
  • Tailoring PHA properties requires enzymes with broader or altered substrate specificities.

Purpose of the Study:

  • To design novel PHA synthase enzymes with potentially enhanced or altered specificities using artificial intelligence.
  • To validate the activity and functionality of computationally designed PHA synthases in a biological system.

Main Methods:

  • A conditional variational autoencoder was employed to generate approximately 10,000 novel PHA synthase sequences.
  • Sequences were selected based on conserved catalytic residues, dimer interface integrity, and structural features.
  • In vivo validation of 16 selected enzyme variants was performed in yeast (Saccharomyces cerevisiae).

Main Results:

  • Two novel PHA synthase variants, with 87 and 98 amino acid substitutions, were successfully designed and synthesized.
  • Both active variants demonstrated the ability to produce poly(hydroxybutyrate) (PHB) when expressed in yeast.
  • The study confirmed the efficacy of AI in creating functional variants of complex dimeric enzymes.

Conclusions:

  • AI-driven protein design is a powerful approach for engineering complex enzymes like PHA synthases.
  • Novel PHA synthases with significant modifications can be generated and shown to be active in vivo.
  • This methodology opens avenues for creating tailored biopolymers with desired material properties.