Evidence map›Paper›PMID 35082289›Full record

ArticleNature communications2022

Engineering the stambomycin modular polyketide synthase yields 37-membered mini-stambomycins.

Li Su, Laurence Hôtel, Cédric Paris, Clara Chepkirui, Alexander O Brachmann, Jörn Piel, Christophe Jacob, Bertrand Aigle, Kira J Weissman

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Li SuUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France.ORCID http://orcid.org/0000-0002-7787-684X
Laurence HôtelUniversité de Lorraine, INRAE, DynAMic, F-54000, Nancy, France.
Cédric ParisUniversité de Lorraine, LIBio, F-54000, Nancy, France.
Clara ChepkiruiInstitute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, 8093, Zurich, Switzerland.
Alexander O BrachmannInstitute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, 8093, Zurich, Switzerland.
Jörn PielInstitute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, 8093, Zurich, Switzerland.
Christophe JacobUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France. christophe.jacob@univ-lorraine.fr.ORCID http://orcid.org/0000-0001-8522-2865
Bertrand AigleUniversité de Lorraine, INRAE, DynAMic, F-54000, Nancy, France. bertrand.aigle@univ-lorraine.fr.ORCID http://orcid.org/0000-0001-5266-5926
Kira J WeissmanUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France. kira.weissman@univ-lorraine.fr.ORCID http://orcid.org/0000-0002-3012-2960

Funding

EPA EP-C-15-004
6 · The paper itself

Abstract

The modular organization of the type I polyketide synthases (PKSs) would seem propitious for rational engineering of desirable analogous. However, despite decades of efforts, such experiments remain largely inefficient. Here, we combine multiple, state-of-the-art approaches to reprogram the stambomycin PKS by deleting seven internal modules. One system produces the target 37-membered mini-stambomycin metabolites - a reduction in chain length of 14 carbons relative to the 51-membered parental compounds - but also substantial quantities of shunt metabolites. Our data also support an unprecedented off-loading mechanism of such stalled intermediates involving the C-terminal thioesterase domain of the PKS. The mini-stambomycin yields are reduced relative to wild type, likely reflecting the poor tolerance of the modules downstream of the modified interfaces to the non-native substrates. Overall, we identify factors contributing to the productivity of engineered whole assembly lines, but our findings also highlight the need for further research to increase production titers.

Indexed as

Metabolic EngineeringAmino Acid SequenceMacrolidesMultienzyme ComplexesPolyketide SynthasesSubstrate SpecificitySynthetic BiologyMacrolidesMultienzyme ComplexesPolyketide Synthases

Identifiers

PMID35082289
PMCPMC8792006

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.