Evidence map›Paper›PMID 34711827›Full record

ArticleNature communications2021

Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering.

Kristin J Adolfsen, Isolde Callihan, Catherine E Monahan, Per Jr Greisen, James Spoonamore, Munira Momin, Lauren E Fitch, Mary Joan Castillo, Lindong Weng, Lauren Renaud and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
10.4field-weighted citation impact, top 1% of its field
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

46 citing papers in PubMed, 91 citations in OpenAlex.

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  13. The gut microbiome connects nutrition and human health.Nature reviews. Gastroenterology & hepatology · 2025
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  20. Bacterial live therapeutics for human diseases.Molecular systems biology · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 1 country.

Kristin J AdolfsenZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Isolde CallihanZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Catherine E MonahanSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-2096-1699
Per Jr GreisenZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
James SpoonamoreZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Munira MominSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA.
Lauren E FitchZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.ORCID http://orcid.org/0000-0002-6360-443X
Mary Joan CastilloSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA.
Lindong WengZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Lauren RenaudSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA.
Carl J WeileZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Jay H KonieczkaZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Teodelinda MirabellaSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA.
Andres Abin-FuentesSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA.
Adam G LawrenceZymergen Inc. (formerly enEvolv Inc.), 100 Acorn Park Drive, Cambridge, MA, 02140, USA.
Vincent M IsabellaSynlogic Inc, 301 Binney St, Cambridge, MA, 02139, USA. vincent@synlogictx.com.ORCID http://orcid.org/0000-0002-5849-3149
enEvolv (United States) · USSynlogic (United States) · USNovo Nordisk (United States) · USSana Biotechnology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In phenylketonuria (PKU) patients, a genetic defect in the enzyme phenylalanine hydroxylase (PAH) leads to elevated systemic phenylalanine (Phe), which can result in severe neurological impairment. As a treatment for PKU, Escherichia coli Nissle (EcN) strain SYNB1618 was developed under Synlogic's Synthetic Biotic™ platform to degrade Phe from within the gastrointestinal (GI) tract. This clinical-stage engineered strain expresses the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL), catalyzing the deamination of Phe to the non-toxic product trans-cinnamate (TCA). In the present work, we generate a more potent EcN-based PKU strain through optimization of whole cell PAL activity, using biosensor-based high-throughput screening of mutant PAL libraries. A lead enzyme candidate from this screen is used in the construction of SYNB1934, a chromosomally integrated strain containing the additional Phe-metabolizing and biosafety features found in SYNB1618. Head-to-head, SYNB1934 demonstrates an approximate two-fold increase in in vivo PAL activity compared to SYNB1618.

Indexed as

Biological TherapyBiosensing TechniquesCinnamatesEscherichia coliEscherichia coli ProteinsHumansPhenylalaninePhenylalanine Ammonia-LyasePhenylketonuriasProtein EngineeringCinnamatesEscherichia coli ProteinsPhenylalaninePhenylalanine Ammonia-Lyase

Identifiers

PMID34711827
PMCPMC8553829
OpenAlexW3209369260

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.