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Signal sequences target enzymes and structural proteins to bacterial microcompartments and are critical for microcompartment formation
Open accessPreprint — published as 10.1128/msphere.00962-24 · Paper page
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 constitutes 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 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.
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Metadata
- Authors
- Johnson, E. R., Kennedy, N. W., Mills, C. E., Liang, S., Chandrasekar, S., Nichols, T. M., Rybnicky, G. A., & Tullman-Ercek, D.
- Affiliations
- Northwestern University (US)
- ORCID
- Venue
- mSphere
- Publisher
- openRxiv
- Published
- 2024-09-25
- Volume
- 10
- Issue
- 5
- Pages
- e0096224-e0096224
- ISSN
- 2379-5042 (ISSN-L)
- PMC
- PMC12108088
- OpenAlex
- W4409484492
- Cited by
- 4
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mSphere (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Science Foundation (1842165, 2021900, 2308691, P41-GM103311, 2150269)
- U.S. Department of Energy (DESC0022180)
- Northwestern University (DGE-1842165)
- National Institutes of Health
- U.S. Army (W52P1J2193023)
- University of California, San Francisco (NIH P41-GM103311, P41-GM103311)
- National Science Foundation of Sri Lanka (DGE-2021900, DMR-2308691, DBI-2150269)
- National Institute of General Medical Sciences (P41GM103311, T32GM140995)
- Division of Materials Research (DMR2308691, 2308691)
- Division of Biological Infrastructure
- National Science Foundation Graduate Research Fellowship Program (DGE‐1842165)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Keywords
- bacterial microcompartments, signal peptide, structural proteins, metabolic engineering
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