Accelerating Biocatalysis Discovery with Machine Learning: A Paradigm Shift in Enzyme Engineering, Discovery, and Design

被引:26
作者
Markus, Braun [1 ]
Christian, Gruber C. [2 ]
Andreas, Krassnigg [2 ]
Arkadij, Kummer [3 ]
Stefan, Lutz [4 ]
Gustav, Oberdorfer [1 ]
Elina, Siirola [5 ]
Radka, Snajdrova [5 ]
机构
[1] Graz Univ Technol, Dept Biochem, A-8010 Graz, Austria
[2] Innophore, Enzyme & Drug Discovery, San Francisco, CA 94111 USA
[3] Moderna Inc, Cambridge, MA 02139 USA
[4] Codexis Inc, Redwood City, CA 94063 USA
[5] Novartis Inst Biomed Res, Global Discovery Chem, CH-4108 Basel, Switzerland
基金
奥地利科学基金会; 欧洲研究理事会;
关键词
biocatalysis; machine learning; enzyme evolution; enzyme optimization; enzyme design; enzymeengineering; DIRECTED EVOLUTION; PROTEIN-STRUCTURE; PREDICTION; PROMISCUITY; MECHANISM; CASCADE;
D O I
10.1021/acscatal.3c03417
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Emerging computational tools promise to revolutionize protein engineering for biocatalytic applications and accelerate the development timelines previously needed to optimize an enzyme to its more efficient variant. For over a decade, the benefits of predictive algorithms have helped scientists and engineers navigate the complexity of functional protein sequence space. More recently, spurred by dramatic advances in underlying computational tools, the promise of faster, cheaper, and more accurate enzyme identification, characterization, and engineering has catapulted terms such as artificial intelligence and machine learning to the must-have vocabulary in the field. This Perspective aims to showcase the current status of applications in pharmaceutical industry and also to discuss and celebrate the innovative approaches in protein science by highlighting their potential in selected recent developments and offering thoughts on future opportunities for biocatalysis. It also critically assesses the technology's limitations, unanswered questions, and unmet challenges.
引用
收藏
页码:14454 / 14469
页数:16
相关论文
共 114 条
  • [1] Review of deep learning: concepts, CNN architectures, challenges, applications, future directions
    Alzubaidi, Laith
    Zhang, Jinglan
    Humaidi, Amjad J.
    Al-Dujaili, Ayad
    Duan, Ye
    Al-Shamma, Omran
    Santamaria, J.
    Fadhel, Mohammed A.
    Al-Amidie, Muthana
    Farhan, Laith
    [J]. JOURNAL OF BIG DATA, 2021, 8 (01)
  • [2] Structure- and Data-Driven Protein Engineering of Transaminases for Improving Activity and Stereoselectivity
    Ao, Yu-Fei
    Pei, Shuxin
    Xiang, Chao
    Menke, Marian J.
    Shen, Lin
    Sun, Chenghai
    Dorr, Mark
    Born, Stefan
    Hohne, Matthias
    Bornscheuer, Uwe T.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2023, 62 (23)
  • [3] Directed Evolution: Bringing New Chemistry to Life
    Arnold, Frances H.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2018, 57 (16) : 4143 - 4148
  • [4] Highlighting Human Enzymes Active in Different Metabolic Pathways and Diseases: The Case Study of EC 1.2.3.1 and EC 2.3.1.9
    Babbi, Giulia
    Baldazzi, Davide
    Savojardo, Castrense
    Martelli, Pier Luigi
    Casadio, Rita
    [J]. BIOMEDICINES, 2020, 8 (08)
  • [5] Accurate prediction of protein structures and interactions using a three-track neural network
    Baek, Minkyung
    DiMaio, Frank
    Anishchenko, Ivan
    Dauparas, Justas
    Ovchinnikov, Sergey
    Lee, Gyu Rie
    Wang, Jue
    Cong, Qian
    Kinch, Lisa N.
    Schaeffer, R. Dustin
    Millan, Claudia
    Park, Hahnbeom
    Adams, Carson
    Glassman, Caleb R.
    DeGiovanni, Andy
    Pereira, Jose H.
    Rodrigues, Andria V.
    van Dijk, Alberdina A.
    Ebrecht, Ana C.
    Opperman, Diederik J.
    Sagmeister, Theo
    Buhlheller, Christoph
    Pavkov-Keller, Tea
    Rathinaswamy, Manoj K.
    Dalwadi, Udit
    Yip, Calvin K.
    Burke, John E.
    Garcia, K. Christopher
    Grishin, Nick V.
    Adams, Paul D.
    Read, Randy J.
    Baker, David
    [J]. SCIENCE, 2021, 373 (6557) : 871 - +
  • [6] Multimodal Machine Learning: A Survey and Taxonomy
    Baltrusaitis, Tadas
    Ahuja, Chaitanya
    Morency, Louis-Philippe
    [J]. IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE, 2019, 41 (02) : 423 - 443
  • [7] Low-N protein engineering with data-efficient deep learning
    Biswas, Surojit
    Khimulya, Grigory
    Alley, Ethan C.
    Esvelt, Kevin M.
    Church, George M.
    [J]. NATURE METHODS, 2021, 18 (04) : 389 - +
  • [8] Catalytic promiscuity in biocatalysis: Using old enzymes to form new bonds and follow new pathways
    Bornscheuer, UT
    Kazlauskas, RJ
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (45) : 6032 - 6040
  • [9] Algorithm-aided engineering of aliphatic halogenase WelO5*for the asymmetric late-stage functionalization of soraphens
    Buechler, Johannes
    Malca, Sumire Honda
    Patsch, David
    Voss, Moritz
    Turner, Nicholas J.
    Bornscheuer, Uwe T.
    Allemann, Oliver
    Le Chapelain, Camille
    Lumbroso, Alexandre
    Loiseleur, Olivier
    Buller, Rebecca
    [J]. NATURE COMMUNICATIONS, 2022, 13 (01)
  • [10] Speeding up enzyme discovery and engineering with ultrahigh-throughput methods
    Bunzel, Hans Adrian
    Garraboul, Xavier
    Pott, Moritz
    Hilvert, Donald
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 2018, 48 : 149 - 156