Directed evolution: new parts and optimized function

By Michael J. Dougherty, Frances H. Arnold. 2009

157 citations recorded by the source corpus.

Summary Constructing novel biological systems that function in a robust and predictable manner requires better methods for discovering new functional molecules and for optimizing their assembly in novel biological contexts. By enabling functional diversification and optimization in the absence of detailed mechanistic understanding, directed evolution is a powerful complement to ‘rational’ engineering approaches. Aided by clever selection schemes, directed evolution has generated new parts for genetic circuits, cell-cell communication systems, and non-natural metabolic pathways in bacteria.

Subfields: Molecular Biology

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Citations in the corpus

The coming of age of de novo protein design (2016, background): “Almost all protein engineering so far has involved the modification of naturally occurring proteins to tune or alter their function using techniques such as directed evolution 5–7 , which involves cycles of generating and selecting variation in the laboratory.”
RamaNet: Computational de novo helical protein backbone design using a long short-term memory generative neural network (2019, background): “Hence why some research groups generated man-made protein designs by altering already existing natural proteins [5], since randomly finding a functionally folded protein from the space of all possible protein sequences is more or less statistically impossible.”
Protein design and variant prediction using autoregressive generative models (2021, background): “ver the past 20 years, success in protein engineering has emerged from two distinct approaches, directed evolution 1,2 and knowledge-based force-ﬁ eld modeling 3,4 . and generating biomolecules with known functions is now a major goal of biotechnology and biomedicine, propelled by our ability to…”
Generating Novel, Designable, and Diverse Protein Structures by Equivariantly Diffusing Oriented Residue Clouds (2023, background): “Protein design methods have historically focused on optimizing functional properties of natural proteins through directed evolution (Dougherty & Arnold, 2009) or through rational design of novel protein sequences that hew closely to known structural motifs (Kuhlman et al., 2003).”
AlphaDesign: A de novo protein design framework based on AlphaFold (2021, methodology): “Established methods for protein engineering have until recently focused on tuning naturally occurring proteins through iterative experimental selection processes such as directed evolution [41–43].”