Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.

The Golden Gate strategy entails the use of type IIS restriction enzymes, which cut outside of their recognition sequence. It enables unrestricted design of unique DNA fragments that can be readily and seamlessly recombined. Successfully employed in other synthetic biology applications, we demonstra...

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Main Authors: Daniela Quaglia, Maximilian C C J C Ebert, Paul F Mugford, Joelle N Pelletier
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171741&type=printable
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author Daniela Quaglia
Maximilian C C J C Ebert
Paul F Mugford
Joelle N Pelletier
author_facet Daniela Quaglia
Maximilian C C J C Ebert
Paul F Mugford
Joelle N Pelletier
author_sort Daniela Quaglia
collection DOAJ
description The Golden Gate strategy entails the use of type IIS restriction enzymes, which cut outside of their recognition sequence. It enables unrestricted design of unique DNA fragments that can be readily and seamlessly recombined. Successfully employed in other synthetic biology applications, we demonstrate its advantageous use to engineer a biocatalyst. Hot-spots for mutations were individuated in three distinct regions of Candida antarctica lipase A (Cal-A), the biocatalyst chosen as a target to demonstrate the versatility of this recombination method. The three corresponding gene segments were subjected to the most appropriate method of mutagenesis (targeted or random). Their straightforward reassembly allowed combining products of different mutagenesis methods in a single round for rapid production of a series of diverse libraries, thus facilitating directed evolution. Screening to improve discrimination of short-chain versus long-chain fatty acid substrates was aided by development of a general, automated method for visual discrimination of the hydrolysis of varied substrates by whole cells.
format Article
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issn 1932-6203
language English
publishDate 2017-01-01
publisher Public Library of Science (PLoS)
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series PLoS ONE
spelling doaj-art-22ccb32669e245bfbd118bd9a69d8e5b2025-08-20T02:45:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017174110.1371/journal.pone.0171741Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.Daniela QuagliaMaximilian C C J C EbertPaul F MugfordJoelle N PelletierThe Golden Gate strategy entails the use of type IIS restriction enzymes, which cut outside of their recognition sequence. It enables unrestricted design of unique DNA fragments that can be readily and seamlessly recombined. Successfully employed in other synthetic biology applications, we demonstrate its advantageous use to engineer a biocatalyst. Hot-spots for mutations were individuated in three distinct regions of Candida antarctica lipase A (Cal-A), the biocatalyst chosen as a target to demonstrate the versatility of this recombination method. The three corresponding gene segments were subjected to the most appropriate method of mutagenesis (targeted or random). Their straightforward reassembly allowed combining products of different mutagenesis methods in a single round for rapid production of a series of diverse libraries, thus facilitating directed evolution. Screening to improve discrimination of short-chain versus long-chain fatty acid substrates was aided by development of a general, automated method for visual discrimination of the hydrolysis of varied substrates by whole cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171741&type=printable
spellingShingle Daniela Quaglia
Maximilian C C J C Ebert
Paul F Mugford
Joelle N Pelletier
Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.
PLoS ONE
title Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.
title_full Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.
title_fullStr Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.
title_full_unstemmed Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.
title_short Enzyme engineering: A synthetic biology approach for more effective library generation and automated high-throughput screening.
title_sort enzyme engineering a synthetic biology approach for more effective library generation and automated high throughput screening
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171741&type=printable
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AT maximilianccjcebert enzymeengineeringasyntheticbiologyapproachformoreeffectivelibrarygenerationandautomatedhighthroughputscreening
AT paulfmugford enzymeengineeringasyntheticbiologyapproachformoreeffectivelibrarygenerationandautomatedhighthroughputscreening
AT joellenpelletier enzymeengineeringasyntheticbiologyapproachformoreeffectivelibrarygenerationandautomatedhighthroughputscreening