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Methanol-essential growth of Escherichia coli.

Abstract：

:Methanol represents an attractive substrate for biotechnological applications. Utilization of reduced one-carbon compounds for growth is currently limited to methylotrophic organisms, and engineering synthetic methylotrophy remains a major challenge. Here we apply an in silico-guided multiple knockout approach to engineer a methanol-essential Escherichia coli strain, which contains the ribulose monophosphate cycle for methanol assimilation. Methanol conversion to biomass was stoichiometrically coupled to the metabolization of gluconate and the designed strain was subjected to laboratory evolution experiments. Evolved strains incorporate up to 24% methanol into core metabolites under a co-consumption regime and utilize methanol at rates comparable to natural methylotrophs. Genome sequencing reveals mutations in genes coding for glutathione-dependent formaldehyde oxidation (frmA), NAD(H) homeostasis/biosynthesis (nadR), phosphopentomutase (deoB), and gluconate metabolism (gntR). This study demonstrates a successful metabolic re-routing linked to a heterologous pathway to achieve methanol-dependent growth and represents a crucial step in generating a fully synthetic methylotrophic organism.

journal_name

Nat Commun

journal_title

Nature communications

authors

Meyer F,Keller P,Hartl J,Gröninger OG,Kiefer P,Vorholt JA

doi

10.1038/s41467-018-03937-y

subject

Has Abstract

pub_date

2018-04-17 00:00:00

pages

1508

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03937-y

journal_volume

9

pub_type

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