Self-driving laboratories to autonomously navigate the protein fitness landscape

Rapp, Jacob T.; Bremer, Bennett J.; Romero, Philip A.

doi:10.1038/s44286-023-00002-4

Self-driving laboratories to autonomously navigate the protein fitness landscape

Journal Article · Thu Jan 11 00:00:00 EST 2024 · Nature Chemical Engineering

DOI:https://doi.org/10.1038/s44286-023-00002-4· OSTI ID:2281045

; Bremer, Bennett J.;

Abstract

Protein engineering has nearly limitless applications across chemistry, energy and medicine, but creating new proteins with improved or novel functions remains slow, labor-intensive and inefficient. Here we present the Self-driving Autonomous Machines for Protein Landscape Exploration (SAMPLE) platform for fully autonomous protein engineering. SAMPLE is driven by an intelligent agent that learns protein sequence–function relationships, designs new proteins and sends designs to a fully automated robotic system that experimentally tests the designed proteins and provides feedback to improve the agent’s understanding of the system. We deploy four SAMPLE agents with the goal of engineering glycoside hydrolase enzymes with enhanced thermal tolerance. Despite showing individual differences in their search behavior, all four agents quickly converge on thermostable enzymes. Self-driving laboratories automate and accelerate the scientific discovery process and hold great potential for the fields of protein engineering and synthetic biology.

View Journal Article

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0018409

OSTI ID:: 2281045

Journal Information:: Nature Chemical Engineering, Journal Name: Nature Chemical Engineering Journal Issue: 1 Vol. 1; ISSN 2948-1198

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (36)

Beyond Ternary OPV: High‐Throughput Experimentation and Self‐Driving Laboratories Optimize Multicomponent Systems Langner, Stefan; Häse, Florian; Perea, José Darío Advanced Materials, Vol. 32, Issue 14 https://doi.org/10.1002/adma.201907801	journal	April 2020
Minding the gaps: The importance of navigating holes in protein fitness landscapes Thomas, Neil; Colwell, Lucy J. Cell Systems, Vol. 12, Issue 11 https://doi.org/10.1016/j.cels.2021.10.004	journal	November 2021
Perspectives for self-driving labs in synthetic biology Martin, Hector G.; Radivojevic, Tijana; Zucker, Jeremy Current Opinion in Biotechnology, Vol. 79 https://doi.org/10.1016/j.copbio.2022.102881	journal	February 2023
Adaptive machine learning for protein engineering Hie, Brian L.; Yang, Kevin K. Current Opinion in Structural Biology, Vol. 72 https://doi.org/10.1016/j.sbi.2021.11.002	journal	February 2022
The Rosetta All-Atom Energy Function for Macromolecular Modeling and Design Alford, Rebecca F.; Leaver-Fay, Andrew; Jeliazkov, Jeliazko R. Journal of Chemical Theory and Computation, Vol. 13, Issue 6 https://doi.org/10.1021/acs.jctc.7b00125	journal	May 2017
Discovering New Chemistry with an Autonomous Robotic Platform Driven by a Reactivity-Seeking Neural Network Caramelli, Dario; Granda, Jarosław M.; Mehr, S. Hessam M. ACS Central Science, Vol. 7, Issue 11 https://doi.org/10.1021/acscentsci.1c00435	journal	November 2021
Opportunities at the Intersection of Synthetic Biology, Machine Learning, and Automation Carbonell, Pablo; Radivojevic, Tijana; García Martín, Héctor ACS Synthetic Biology, Vol. 8, Issue 7 https://doi.org/10.1021/acssynbio.8b00540	journal	July 2019
Cloud labs: where robots do the research Arnold, Carrie Nature, Vol. 606, Issue 7914 https://doi.org/10.1038/d41586-022-01618-x	journal	June 2022
Functional genomic hypothesis generation and experimentation by a robot scientist King, Ross D.; Whelan, Kenneth E.; Jones, Ffion M. Nature, Vol. 427, Issue 6971 https://doi.org/10.1038/nature02236	journal	January 2004
A diverse family of thermostable cytochrome P450s created by recombination of stabilizing fragments Li, Yougen; Drummond, D. Allan; Sawayama, Andrew M. Nature Biotechnology, Vol. 25, Issue 9 https://doi.org/10.1038/nbt1333	journal	August 2007
Exploring protein fitness landscapes by directed evolution Romero, Philip A.; Arnold, Frances H. Nature Reviews Molecular Cell Biology, Vol. 10, Issue 12 https://doi.org/10.1038/nrm2805	journal	December 2009
Towards a fully automated algorithm driven platform for biosystems design HamediRad, Mohammad; Chao, Ran; Weisberg, Scott Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13189-z	journal	November 2019
Machine learning-guided acyl-ACP reductase engineering for improved in vivo fatty alcohol production Greenhalgh, Jonathan C.; Fahlberg, Sarah A.; Pfleger, Brian F. Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-25831-w	journal	October 2021
AlphaFlow: autonomous discovery and optimization of multi-step chemistry using a self-driven fluidic lab guided by reinforcement learning Volk, Amanda A.; Epps, Robert W.; Yonemoto, Daniel T. Nature Communications, Vol. 14, Issue 1 https://doi.org/10.1038/s41467-023-37139-y	journal	March 2023
A mobile robotic chemist Burger, Benjamin; Maffettone, Phillip M.; Gusev, Vladimir V. Nature, Vol. 583, Issue 7815 https://doi.org/10.1038/s41586-020-2442-2	journal	July 2020
Deep diversification of an AAV capsid protein by machine learning Bryant, Drew H.; Bashir, Ali; Sinai, Sam Nature Biotechnology, Vol. 39, Issue 6 https://doi.org/10.1038/s41587-020-00793-4	journal	February 2021
Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics Bedbrook, Claire N.; Yang, Kevin K.; Robinson, J. Elliott Nature Methods, Vol. 16, Issue 11 https://doi.org/10.1038/s41592-019-0583-8	journal	October 2019
An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals Carbonell, Pablo; Jervis, Adrian J.; Robinson, Christopher J. Communications Biology, Vol. 1, Issue 1 https://doi.org/10.1038/s42003-018-0076-9	journal	June 2018
The rise of self-driving labs in chemical and materials sciences Abolhasani, Milad; Kumacheva, Eugenia Nature Synthesis, Vol. 2, Issue 6 https://doi.org/10.1038/s44160-022-00231-0	journal	January 2023
A self-driving laboratory designed to accelerate the discovery of adhesive materials Rooney, Michael B.; MacLeod, Benjamin P.; Oldford, Ryan Digital Discovery, Vol. 1, Issue 4 https://doi.org/10.1039/D2DD00029F	journal	January 2022
Navigating the protein fitness landscape with Gaussian processes Romero, P. A.; Krause, A.; Arnold, F. H. Proceedings of the National Academy of Sciences, Vol. 110, Issue 3 https://doi.org/10.1073/pnas.1215251110	journal	December 2012
Dissecting enzyme function with microfluidic-based deep mutational scanning Romero, Philip A.; Tran, Tuan M.; Abate, Adam R. Proceedings of the National Academy of Sciences, Vol. 112, Issue 23 https://doi.org/10.1073/pnas.1422285112	journal	May 2015
Closed-loop cycles of experiment design, execution, and learning accelerate systems biology model development in yeast Coutant, Anthony; Roper, Katherine; Trejo-Banos, Daniel Proceedings of the National Academy of Sciences, Vol. 116, Issue 36 https://doi.org/10.1073/pnas.1900548116	journal	August 2019
nhmmer: DNA homology search with profile HMMs Wheeler, T. J.; Eddy, S. R. Bioinformatics, Vol. 29, Issue 19 https://doi.org/10.1093/bioinformatics/btt403	journal	July 2013
Site-directed protein recombination as a shortest-path problem Endelman, J. B.; Silberg, J. J.; Wang, Z. -G. Protein Engineering Design and Selection, Vol. 17, Issue 7 https://doi.org/10.1093/protein/gzh067	journal	August 2004
Consensus protein design Porebski, Benjamin T.; Buckle, Ashley M. Protein Engineering Design and Selection, Vol. 29, Issue 7 https://doi.org/10.1093/protein/gzw015	journal	June 2016
Taking the Human Out of the Loop: A Review of Bayesian Optimization Shahriari, Bobak; Swersky, Kevin; Wang, Ziyu Proceedings of the IEEE, Vol. 104, Issue 1 https://doi.org/10.1109/JPROC.2015.2494218	journal	January 2016
A beta-glucosidase gene (bgl3) from Streptomyces sp. strain QM-B814. Molecular cloning, nucleotide sequence, purification and characterization of the encoded enzyme, a new member of family 1 glycosyl hydrolases Perez-Pons, Josep A.; Cayetano, Antonio; Rebordosa, Xavier European Journal of Biochemistry, Vol. 223, Issue 2 https://doi.org/10.1111/j.1432-1033.1994.tb19025.x	journal	July 1994
Self-driving laboratory for accelerated discovery of thin-film materials MacLeod, B. P.; Parlane, F. G. L.; Morrissey, T. D. Science Advances, Vol. 6, Issue 20 https://doi.org/10.1126/sciadv.aaz8867	journal	May 2020
The Automation of Science King, Ross D.; Rowland, Jem; Oliver, Stephen G. Science, Vol. 324, Issue 5923 https://doi.org/10.1126/science.1165620	journal	April 2009
Robust deep learning–based protein sequence design using ProteinMPNN Dauparas, J.; Anishchenko, I.; Bennett, N. Science, Vol. 378, Issue 6615 https://doi.org/10.1126/science.add2187	journal	October 2022
Combinatorial assembly and design of enzymes Lipsh-Sokolik, R.; Khersonsky, O.; Schröder, S. P. Science, Vol. 379, Issue 6628 https://doi.org/10.1126/science.ade9434	journal	January 2023
Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450 Otey, Christopher R.; Landwehr, Marco; Endelman, Jeffrey B. PLoS Biology, Vol. 4, Issue 5 https://doi.org/10.1371/journal.pbio.0040112	journal	April 2006
A One Pot, One Step, Precision Cloning Method with High Throughput Capability Engler, Carola; Kandzia, Romy; Marillonnet, Sylvestre PLoS ONE, Vol. 3, Issue 11, Article No. e3647 https://doi.org/10.1371/journal.pone.0003647	journal	November 2008
Thermal stability and kinetic constants for 129 variants of a family 1 glycoside hydrolase reveal that enzyme activity and stability can be separately designed Carlin, Dylan Alexander; Hapig-Ward, Siena; Chan, Bill Wayne PLOS ONE, Vol. 12, Issue 5 https://doi.org/10.1371/journal.pone.0176255	journal	May 2017
Levels of autonomy in synthetic biology engineering Beal, Jacob; Rogers, Miles Molecular Systems Biology, Vol. 16, Issue 12 https://doi.org/10.15252/msb.202010019	journal	December 2020

Similar Records

A generalized platform for artificial intelligence-powered autonomous enzyme engineering

Journal Article · Mon Jun 30 20:00:00 EDT 2025 · Nature Communications · OSTI ID:2574786

Engineering PHL7 for Improved Poly(Ethylene Terephthalate) Depolymerization via Rational Design and Directed Evolution

Journal Article · Mon May 26 00:00:00 EDT 2025 · Chem Catalysis · OSTI ID:2574707

Self-driving laboratories to autonomously navigate the protein fitness landscape

Citation Formats

References (36)

Similar Records

Related Subjects