Combinatorial assembly platform enabling engineering of genetically stable metabolic pathways in cyanobacteria.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
accepted:
02
09
2021
revised:
18
08
2021
received:
23
04
2021
pubmed:
24
9
2021
medline:
11
1
2022
entrez:
23
9
2021
Statut:
ppublish
Résumé
Cyanobacteria are simple, efficient, genetically-tractable photosynthetic microorganisms which in principle represent ideal biocatalysts for CO2 capture and conversion. However, in practice, genetic instability and low productivity are key, linked problems in engineered cyanobacteria. We took a massively parallel approach, generating and characterising libraries of synthetic promoters and RBSs for the cyanobacterium Synechocystis sp. PCC 6803, and assembling a sparse combinatorial library of millions of metabolic pathway-encoding construct variants. Genetic instability was observed for some variants, which is expected when variants cause metabolic burden. Surprisingly however, in a single combinatorial round without iterative optimisation, 80% of variants chosen at random and cultured photoautotrophically over many generations accumulated the target terpenoid lycopene from atmospheric CO2, apparently overcoming genetic instability. This large-scale parallel metabolic engineering of cyanobacteria provides a new platform for development of genetically stable cyanobacterial biocatalysts for sustainable light-driven production of valuable products directly from CO2, avoiding fossil carbon or competition with food production.
Identifiants
pubmed: 34554258
pii: 6374482
doi: 10.1093/nar/gkab791
pmc: PMC8643660
doi:
Substances chimiques
Lycopene
SB0N2N0WV6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e123Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M002454/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011321/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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