Systems and Methods for Continuous Evolution of Enzymes.

Autor: Chen A; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138, USA E-mail: Dr David A. Weitz: E-mail: Dr. Karla Milcic., Zhang XD; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138, USA E-mail: Dr David A. Weitz: E-mail: Dr. Karla Milcic., Đelmaš AĐ; University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000, Belgrade, Serbia., Weitz DA; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138, USA E-mail: Dr David A. Weitz: E-mail: Dr. Karla Milcic.; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA, 02115, USA.; Department of Physics, Harvard University, Cambridge, MA, 02138, USA., Milcic K; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138, USA E-mail: Dr David A. Weitz: E-mail: Dr. Karla Milcic.; University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000, Belgrade, Serbia.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Aug 01; Vol. 30 (43), pp. e202400880. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1002/chem.202400880
Abstrakt: Directed evolution generates novel biomolecules with desired functions by iteratively diversifying the genetic sequence of wildtype biomolecules, relaying the genetic information to the molecule with function, and selecting the variants that progresses towards the properties of interest. While traditional directed evolution consumes significant labor and time for each step, continuous evolution seeks to automate all steps so directed evolution can proceed with minimum human intervention and dramatically shortened time. A major application of continuous evolution is the generation of novel enzymes, which catalyze reactions under conditions that are not favorable to their wildtype counterparts, or on altered substrates. The challenge to continuously evolve enzymes lies in automating sufficient, unbiased gene diversification, providing selection for a wide array of reaction types, and linking the genetic information to the phenotypic function. Over years of development, continuous evolution has accumulated versatile strategies to address these challenges, enabling its use as a general tool for enzyme engineering. As the capability of continuous evolution continues to expand, its impact will increase across various industries. In this review, we summarize the working mechanisms of recently developed continuous evolution strategies, discuss examples of their applications focusing on enzyme evolution, and point out their limitations and future directions.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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