Repository logo
 

An efficient method to assemble linear DNA templates for in vitro screening and selection systems.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Stein, Viktor 
Hollfelder, Florian  ORCID logo  https://orcid.org/0000-0002-1367-6312

Abstract

A method is presented to assemble a gene of interest into a linear DNA template with all the components necessary for in vitro transcription and translation in approximately 90 min. Assembly is achieved using a coupled uracil excision-ligation strategy based on USER Enzyme and T4 DNA ligase, which allows the simultaneous and seamless assembly of three different PCR products. The method is suitable for screening and selection systems of very high throughput as up to 10(11) molecules can be efficiently assembled and purified in reaction volumes of 100 microl. The method is exemplified with the gene coding for a mutant version of O(6)-alkylguanine alkyltransferase, which is efficiently assembled with an N-terminal peptide tag and its 5'- and 3'-untranslated regions that include a T7 promoter, ribosome binding site and T7 terminator. The utility of the method is further corroborated by assembling error-prone PCR libraries and regenerating templates following model affinity selections. This fast and robust method should find widespread application in directed evolution for the assembly of gene libraries and the regeneration of linear DNA templates between successive screening and selection cycles.

Description

Keywords

5' Untranslated Regions, DNA, DNA Ligases, Directed Molecular Evolution, Gene Library, Genes, O(6)-Methylguanine-DNA Methyltransferase, Polymerase Chain Reaction, Protein Biosynthesis, Templates, Genetic, Transcription, Genetic, Uracil

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

37

Publisher

Oxford University Press (OUP)