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Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome

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Title: Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome
Authors: Blount, B
Gowers, G
Ho, JCH
Ledesma-Amaro, R
Jovicevic, D
McKiernan, R
Xie, ZX
Li, BZ
Yuan, YJ
Ellis, T
Item Type: Journal Article
Abstract: Synthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet, it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This new synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques.
Issue Date: 22-May-2018
Date of Acceptance: 23-Jan-2018
URI: http://hdl.handle.net/10044/1/56653
DOI: 10.1038/s41467-018-03143-w
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 9
Issue: 1
Copyright Statement: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article ’ s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article ’ s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/K019791/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
SACCHAROMYCES-CEREVISIAE
EUKARYOTIC CHROMOSOME
DIVERSITY
EXPRESSION
PATHWAYS
OPTIMIZATION
GENOMICS
TOOLKIT
BIOLOGY
XYLOSE
Base Sequence
Benchmarking
Chromosomes, Fungal
Clone Cells
Gene Editing
Gene Expression Regulation, Fungal
Genes, Synthetic
Genome, Fungal
High-Throughput Nucleotide Sequencing
Indoles
Metabolic Engineering
Metabolic Networks and Pathways
Penicillins
Plasmids
Recombination, Genetic
Saccharomyces cerevisiae
Xylose
Clone Cells
Chromosomes, Fungal
Saccharomyces cerevisiae
Penicillins
Indoles
Xylose
Gene Expression Regulation, Fungal
Recombination, Genetic
Base Sequence
Genome, Fungal
Genes, Synthetic
Plasmids
Benchmarking
Metabolic Networks and Pathways
High-Throughput Nucleotide Sequencing
Metabolic Engineering
Gene Editing
Publication Status: Published
Article Number: 1932
Appears in Collections:Bioengineering
Faculty of Engineering