A5090060799- Cyclopropane Reaction Mechanisms
- Enzyme Catalysis and Immobilization
- Metal-Catalyzed Oxygenation Mechanisms
- Asymmetric Hydrogenation and Catalysis
- Synthesis and Catalytic Reactions
- CRISPR and Genetic Engineering
- Crystallization and Solubility Studies
- Fluorine in Organic Chemistry
- Protein Structure and Dynamics
- X-ray Diffraction in Crystallography
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 and COVID-19 Research
- DNA and Biological Computing
- Neurobiology and Insect Physiology Research
- Antimicrobial Peptides and Activities
- Amino Acid Enzymes and Metabolism
- Microbial metabolism and enzyme function
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- Insect and Pesticide Research
- Enzyme Structure and Function
- Wastewater Treatment and Nitrogen Removal
- Biochemical and Molecular Research
Codexis (United States)
2021-2025
California Institute of Technology
2017-2022
University of California, Los Angeles
2022
CIC bioGUNE
2022
Johns Hopkins University
2022
Universität Greifswald
2016
University of Wisconsin–Madison
2013
Molnupiravir (MK-4482) is an investigational antiviral agent that under development for the treatment of COVID-19. Given potential high demand and urgency this compound, it was critical to develop a short sustainable synthesis from simple raw materials would minimize time needed manufacture supply molnupiravir. The route reported here enabled through invention novel biocatalytic cascade featuring engineered ribosyl-1-kinase uridine phosphorylase. These enzymes were deployed with...
Developing catalysts that produce each stereoisomer of a desired product selectively is longstanding synthetic challenge. Biochemists have addressed this challenge by screening nature's diversity to discover enzymes catalyze the formation complementary stereoisomers. We show here same approach can be applied new-to-nature enzymatic reaction, alkene cyclopropanation via carbene transfer. By diverse native and engineered heme proteins, we identified globins serine-ligated "P411" variants...
The repurposing of hemoproteins for non-natural carbene transfer activities has generated enzymes functions previously accessible only to chemical catalysts. With constrained specific substrate classes, however, the synthetic utility these new biocatalysts been limited. To expand capabilities biocatalysis, we engineered variants Cytochrome P450BM3 that catalyze cyclopropanation heteroatom-bearing alkenes, providing valuable nitrogen-, oxygen-, and sulfur-substituted cyclopropanes. Four or...
The crucial molecular events accompanying protein folding in the cell are still largely unexplored. As nascent polypeptides emerge from ribosomal exit tunnel, they come close proximity with highly negatively charged surface. How is polypeptide influenced by surface? We address this question via intrinsically disordered PIR and a number of its variably mutants. Two different populations identified: one spatially biased, other dynamic. more emerging ribosome richer extremely dynamic...
Transition-metal catalysis is a powerful tool for the construction of chemical bonds. Here we show that Pseudomonas savastanoi ethylene-forming enzyme, non-heme iron can catalyze olefin aziridination and nitrene C–H insertion, these activities be improved by directed evolution. The center allows facile modification primary coordination sphere addition metal-coordinating molecules, enabling control over enzyme activity selectivity using small molecules.
While biocatalysis is increasingly incorporated into drug development pipelines, it less commonly used in the early stages of discovery. By engineering a protein to produce chiral motif with derivatizable functional handle, biocatalysts can be help generate diverse building blocks for Here we show two variants Rhodothermus marinus nitric oxide dioxygenase (RmaNOD) catalyze formation cis- and trans-diastereomers pinacolboronate-substituted cyclopropane which readily derivatized stereopure blocks.
Abstract Trifluoromethyl‐substituted cyclopropanes (CF 3 ‐CPAs) constitute an important class of compounds for drug discovery. While several methods have been developed synthesis trans ‐CF ‐CPAs, stereoselective production corresponding cis ‐diastereomers remains a formidable challenge. We report biocatalyst diastereo‐ and enantio‐selective ‐CPAs with activity on variety alkenes. found that engineered protoglobin from Aeropyrnum pernix ( Ape Pgb) can catalyze this unusual reaction at...
Enzymatic DNA synthesis, using stepwise nucleotide addition catalyzed by template-independent polymerases, promises higher efficiency, quality, and sustainability than today's industry-standard phosphoramidite-based processes. We report the directed evolution of a terminal deoxynucleotidyl transferase that uses 3'-phosphate-blocked 2'-deoxynucleoside triphosphates (dNTPs) to control polymerization reaction. Over 32 iterative rounds laboratory evolution, 80 amino acid...
<p>Stereodivergent syntheses leading to the different stereoisomers of a product are useful in discovery and testing drugs agrochemicals. A longstanding challenge catalysis, developing sets stereodivergent catalysts is often solved for enzymes by screening Nature’s diversity biocatalysts with complementary stereoselectivities. Here, protein has been leveraged develop reaction not known biology, cyclopropanation via carbene transfer. By diverse native engineered heme proteins, we...
Abstract Enzymatic DNA synthesis, using stepwise nucleotide addition catalyzed by template-independent polymerases, promises higher efficiency, quality, and sustainability than today’s industry standard phosphoramidite-based processes. We report on the directed evolution of a terminal deoxynucleotidyl transferase that uses 3’-phosphate blocked dNTPs to control polymerization reaction demonstrates high activity for these modified substrates improved template promiscuity thermostability.
Stereodivergent syntheses leading to the different stereoisomers of a product are useful in discovery and testing drugs agrochemicals. A longstanding challenge catalysis, developing sets stereodivergent catalysts is often solved for enzymes by screening Nature’s diversity biocatalysts with complementary stereoselectivities. Here, protein has been leveraged develop reaction not known biology, cyclopropanation via carbene transfer. By diverse native engineered heme proteins, we identified...
Transition-metal catalysis is a powerful tool for the construction of chemical bonds. Here we show that non-heme iron enzyme can catalyze olefin aziridination and nitrene C–H insertion, these activities be improved by directed evolution. The center allows facile modification primary coordination sphere addition metal-coordinating molecules, enabling control over activity selectivity using small molecules.
Transition-metal catalysis is a powerful tool for the construction of chemical bonds. Here we show that non-heme iron enzyme can catalyze olefin aziridination and nitrene C–H insertion, these activities be improved by directed evolution. The center allows facile modification primary coordination sphere addition metal-coordinating molecules, enabling control over activity selectivity using small molecules.
Abstract Trifluoromethyl‐substituted cyclopropanes (CF 3 ‐CPAs) constitute an important class of compounds for drug discovery. While several methods have been developed synthesis trans ‐CF ‐CPAs, stereoselective production corresponding cis ‐diastereomers remains a formidable challenge. We report biocatalyst diastereo‐ and enantio‐selective ‐CPAs with activity on variety alkenes. found that engineered protoglobin from Aeropyrnum pernix ( Ape Pgb) can catalyze this unusual reaction at...