Publications and Whitepapers

Synthetic Biology for Chemical Production

Alexandre Zanghellini, Arzeda’s CEO, penned an overview of both the current and the future impact of synthetic biology upon the chemicals industry. It highlights the opportunities that can be opened through the simultaneous advance of several technologies- improved fermentation strategies, development of biological FABs, designer biocatalysts, and improved synthetic DNA. Arzeda is at the forefront

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INVISTA receives patent for bio-derived raw materials technology developed through collaboration with Arzeda

…Alexandre Zanghellini, co-founder and chief executive officer at Arzeda, said, “The issuance of this patent is yet another example of the power of combining Arzeda’s computational protein design technology Archytas™ with experimental screening to rapidly design synthetic enzymes. With INVISTA’s expertise in biotechnology and industrial scale-up, we are confident this collaboration will lead to advanced

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SBOL Visual: A Graphical Language for Genetic Designs

One of the team members at Arzeda recently published a paper advancing a standard for a common language for use across synthetic biology. Well done, Michal!

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de novo computational enzyme design

Zanghellini, A. Curr Opin Biotechnol. 2014: 29C:132-138 Abstract: Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will

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Progress and Challenges in Computational Protein Design

Ban YA, Röthlisberger-Grabs D, Althoff EA, and Zanghellini A. Protein Engineering Handbook, Volume 3, 2012: 363-406 Abstract: The tremendous increase in the amount of protein structural information acquired during the past four decades has opened new avenues – first and foremost for the detailed understanding of protein function at the molecular level. The rational, structure-based engineering

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Structural analyses of covalent enzyme-substrate analog complexes reveal strengths and limitations of de novo enzyme design

Wang L, Althoff EA, et al. J Mol Biol. 2012: 415:615-25 Abstract: We report the cocrystal structures of a computationally designed and experimentally optimized retro-aldol enzyme with covalently bound substrate analogs. The structure with a covalently bound mechanism-based inhibitor is similar to, but not identical with, the design model, with an RMSD of 1.4 Å

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Robust design and optimization of retroaldol enzymes

Althoff EA, et al. Protein Sci. 2012: 21:717-26 Abstract: Enzyme catalysts of a retroaldol reaction have been generated by computational design using a motif that combines a lysine in a nonpolar environment with water-mediated stabilization of the carbinolamine hydroxyl and β-hydroxyl groups. Here, we show that the design process is robust and repeatable, with 33

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Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction

Zanghellini, A. et al.Science 2010: 329: 309-313 Abstract: The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing

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Exploitation of binding energy for catalysis and design

Thyme S.B. et al., Nature 2009; 461: 1300-1304 PubMed Abstract: Enzymes use substrate-binding energy both to promote ground-state association and to stabilize the reaction transition state selectively. The monomeric homing endonuclease I-AniI cleaves with high sequence specificity in the centre of a 20-base-pair (bp) DNA target site, with the amino (N)-terminal domain of the enzyme making

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Blind docking of pharmaceutically relevant compounds using RosettaLigand

8 Davis I.W. et al., JMB 2009; 385: 381-392 PubMed Abstract: It is difficult to properly validate algorithms that dock a small molecule ligand into its protein receptor using data from the public domain: the predictions are not blind because the correct binding mode is already known, and public test cases may not be representative

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RosettaLigand docking with full ligand and receptor flexibility

Davis I.W. et al., JMB 2009; 385: 381-392 PubMed Abstract: Computational docking of small-molecule ligands into protein receptors is an important tool for modern drug discovery. Although conformational adjustments are frequently observed between the free and ligand-bound states, the conformational flexibility of the protein is typically ignored in protein-small molecule docking programs. We previously described

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Kemp elimination catalysts by computational enzyme design

Röthlisberger D. et al., Nature 2008; 453: 190-195 PubMed Abstract: The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis. Here we describe the computational design of eight enzymes that use two different catalytic motifs to

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De novo computational design of retro-aldol enzymes

Althoff, E.A. et al., Science 2008; 319: 1387-1391 PubMed Abstract: The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the

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New algorithms and an in silico benchmark for computational enzyme design

Zanghellini, A. et al., Protein Sci. 2006; 15: 2785-2794 PubMed Abstract: The creation of novel enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Here we describe two new algorithms for enzyme design that employ hashing techniques to allow searching through large numbers of protein scaffolds for optimal

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Computational redesign of endonuclease DNA binding and cleavage specificity

Ashworth J. et al., Nature 2006; 441: 656-659 PubMed Abstract: The reprogramming of DNA-binding specificity is an important challenge for computational protein design that tests current understanding of protein-DNA recognition, and has considerable practical relevance for biotechnology and medicine. Here we describe the computational redesign of the cleavage specificity of the intron-encoded homing endonuclease I-MsoI

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Computational thermostabilization of an enzyme

Korkegian, A. et al., Science 2005; 308: 857-860 PubMed Abstract: Thermostabilizing an enzyme while maintaining its activity for industrial or biomedical applications can be difficult with traditional selection methods. We describe a rapid computational approach that identified three mutations within a model enzyme that produced a 10 degrees C increase in apparent melting temperature T(m) and

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