A5049633522- Microbial Natural Products and Biosynthesis
- Plant-Microbe Interactions and Immunity
- Synthetic Organic Chemistry Methods
- Evolution and Genetic Dynamics
- Enzyme Catalysis and Immobilization
- Fungal Biology and Applications
- Evolutionary Algorithms and Applications
- Microbial Metabolism and Applications
- Plant biochemistry and biosynthesis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Gene Regulatory Network Analysis
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
California Institute of Technology
2025
Joint BioEnergy Institute
2018-2020
Lawrence Berkeley National Laboratory
2018-2020
Abstract Directed evolution (DE) is a powerful tool to optimize protein fitness for specific application. However, DE can be inefficient when mutations exhibit non-additive, or epistatic, behavior. Here, we present Active Learning-assisted Evolution (ALDE), an iterative machine learning-assisted workflow that leverages uncertainty quantification explore the search space of proteins more efficiently than current methods. We apply ALDE engineering landscape challenging DE: optimization five...
ABSTRACT Directed evolution (DE) is a powerful tool to optimize protein fitness for specific application. However, DE can be inefficient when mutations exhibit non-additive, or epistatic, behavior. Here, we present Active Learning-assisted Evolution (ALDE), an iterative machine learning-assisted workflow that leverages uncertainty quantification explore the search space of proteins more efficiently than current methods. We apply ALDE engineering landscape challenging DE: optimization five...
Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge re-engineering a partially reductive PKS module produce saturated β-carbon through loop (RL) exchange. In this work, we sought establish that chemoinformatics, field traditionally used in drug discovery, offers viable strategy for RL exchanges. We first introduced set of donor RLs diverse genetic origin chemical substrates into the...
To reduce the effects of greenhouse gas emissions on climate change, scientific efforts have sought to develop biofuels and bio‐based commodity chemicals as petrochemical replacements primarily for their environmental benefits. As biological design space is far greater than chemical synthesis, there has been a drive leverage this ability create replace fine specialty chemicals. While polyketide synthases traditionally studied biosynthesis pharmaceutical chemicals, unique advantages...
Abstract Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge in PKS design a partially reductive module produce saturated β-carbon through loop exchange. In this work, we sought establish that chemoinformatics, field traditionally used drug discovery, could provide viable strategy exchanges. We first introduced set of donor loops diverse genetic origin chemical substrate structures...
Abstract Traditionally engineered to produce novel bioactive molecules, Type I modular polyketide synthases (PKSs) could be as a new biosynthetic platform for the production of de novo fuels, commodity chemicals, and specialty chemicals. Previously, our investigations manipulated first module lipomycin PKS short chain ketones, 3-hydroxy acids, saturated, branched carboxylic acids. Building upon this work, we have expanded multi-modular systems by engineering two modules generate unnatural...