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

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 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Blount BA,Gowers GF,Ho JCH,Ledesma-Amaro R,Jovicevic D,McKiernan RM,Xie ZX,Li BZ,Yuan YJ,Ellis T

doi

10.1038/s41467-018-03143-w

subject

Has Abstract

pub_date

2018-05-22 00:00:00

pages

1932

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03143-w

journal_volume

9

pub_type

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