Machine-Learning-Guided Mutagenesis for Directed Evolution of Fluorescent Proteins

Autor: Misaki Oikawa, Yutaka Saito, Teppei Niide, Hikaru Nakazawa, Tomoshi Kameda, Mitsuo Umetsu, Koji Tsuda
Rok vydání: 2018
Předmět:
Zdroj: ACS synthetic biology. 7(9)
ISSN: 2161-5063
Popis: Molecular evolution based on mutagenesis is widely used in protein engineering. However, optimal proteins are often difficult to obtain due to a large sequence space. Here, we propose a novel approach that combines molecular evolution with machine learning. In this approach, we conduct two rounds of mutagenesis where an initial library of protein variants is used to train a machine-learning model to guide mutagenesis for the second-round library. This enables us to prepare a small library suited for screening experiments with high enrichment of functional proteins. We demonstrated a proof-of-concept of our approach by altering the reference green fluorescent protein (GFP) so that its fluorescence is changed into yellow. We successfully obtained a number of proteins showing yellow fluorescence, 12 of which had longer wavelengths than the reference yellow fluorescent protein (YFP). These results show the potential of our approach as a powerful method for directed evolution of fluorescent proteins.
Databáze: OpenAIRE