In situ intein-mediated multiprotein assembly via engineered cross-species consortia
Inteins can connect flanking external proteins into a new protein fragment and excise themselves. Here, we report the in situ splicing of proteins by engineered microbial consortia. This study pioneers a programmable microbial consortia platform enabling in situ protein splicing through split intein...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1529655/full |
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| Summary: | Inteins can connect flanking external proteins into a new protein fragment and excise themselves. Here, we report the in situ splicing of proteins by engineered microbial consortia. This study pioneers a programmable microbial consortia platform enabling in situ protein splicing through split intein-mediated assembly. Engineered Escherichia coli with the ePop autolysis system release intein-fused protein fragments via synchronized lysis, while Pichia pastoris secretes complementary domains, enabling extracellular reconstitution directly in culture. With the application of integrating quorum-sensing controls and eukaryotic secretion pathways, this approach bypasses in vitro purification, supporting scalable one-pot synthesis of multiple functional proteins. The platform’s versatility in logic computation and antibiotic resistance engineering highlights its potential for adaptive biomanufacturing and context-aware biomaterial design. |
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| ISSN: | 2296-4185 |