Evidence map›Paper›PMID 40237445›Full record

ArticlemSphere2025

Signal sequences target enzymes and structural proteins to bacterial microcompartments and are critical for microcompartment formation.

Elizabeth R Johnson, Nolan W Kennedy, Carolyn E Mills, Shiqi Liang, Swetha Chandrasekar, Taylor M Nichols, Grant A Rybnicky, Danielle Tullman-Ercek

Abstract read
In one paragraph

Article in mSphere, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Elizabeth R JohnsonDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.ORCID 0000-0001-7923-6881
Nolan W KennedyDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
Carolyn E MillsDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
Shiqi LiangCenter for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
Swetha ChandrasekarCenter for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
Taylor M NicholsDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
Grant A RybnickyCenter for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
Danielle Tullman-ErcekDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.ORCID 0000-0001-6734-480X

Funding

Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Molecular Biophysics Training Program at Northwestern UniversityT32GM140995 · NIGMS · NORTHWESTERN UNIVERSITY · PI Heather Wendy Pinkett, Reza Vafabakhsh · 2021 to 2026
$2.5M
National Science Foundation DBI-2150269National Science Foundation DGE-2021900National Science Foundation DMR-2308691NIGMS NIH HHS P41 GM103311NIGMS NIH HHS T32 GM140995NIH HHS 5T32GM140995-04NSF | National Science Foundation Graduate Research Fellowship Program (GRFP) DGE-1842165U.S. Army W52P1J2193023U.S. Department of Energy DE-SC0022180
6 · The paper itself

Abstract

Spatial organization of pathway enzymes has emerged as a promising tool to address several challenges in metabolic engineering, such as flux imbalances and off-target product formation. Bacterial microcompartments (MCPs) are a spatial organization strategy used natively by many bacteria to encapsulate metabolic pathways that produce toxic, volatile intermediates. Several recent studies have focused on engineering MCPs to encapsulate heterologous pathways of interest, but how this engineering affects MCP assembly and function is poorly understood. In this study, we investigated the role of signal sequences, short domains that target proteins to the MCP core, in the assembly of 1,2-propanediol utilization (Pdu) MCPs. We characterized two novel Pdu signal sequences on the structural proteins PduM and PduB, which constitute the first report of metabolosome signal sequences on structural proteins rather than enzymes. We then explored the role of enzymatic and structural Pdu signal sequences on MCP assembly by deleting their encoding sequences from the genome alone and in combination. Deleting enzymatic signal sequences decreased the MCP formation, but this defect could be recovered in some cases by overexpressing genes encoding the knocked-out signal sequence fused to a heterologous protein. By contrast, deleting structural signal sequences caused similar defects to knocking out the genes encoding the full-length PduM and PduB proteins. Our results contribute to a growing understanding of how MCPs form and function in bacteria and provide strategies to mitigate assembly disruption when encapsulating heterologous pathways in MCPs.IMPORTANCESpatially organizing biosynthetic pathway enzymes is a promising strategy to increase pathway throughput and yield. Bacterial microcompartments (MCPs) are proteinaceous organelles that many bacteria natively use as a spatial organization strategy to encapsulate niche metabolic pathways, providing significant metabolic benefits. Encapsulating heterologous pathways of interest in MCPs could confer these benefits to industrially relevant pathways. Here, we investigate the role of signal sequences, short domains that target proteins for encapsulation in MCPs, in the assembly of 1,2-propanediol utilization (Pdu) MCPs. We characterize two novel signal sequences on structural proteins, constituting the first Pdu signal sequences found on structural proteins rather than enzymes, and perform knockout studies to compare the impacts of enzymatic and structural signal sequences on MCP assembly. Our results demonstrate that enzymatic and structural signal sequences play critical but distinct roles in Pdu MCP assembly and provide design rules for engineering MCPs while minimizing disruption to MCP assembly.

Indexed as

Bacterial ProteinsOrganellesProtein Sorting SignalsEscherichia coliMetabolic EngineeringMetabolic Networks and PathwaysPropylene GlycolBacterial ProteinsPropylene GlycolProtein Sorting Signals1,2-propanediol utilization microcompartmentbacterial microcompartmentsprotein encapsulationself-assembly

Identifiers

PMID40237445
PMCPMC12108088

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.