Conditional Split Inteins: Adaptable Tools for Programming Protein Functions

Shepherd, Callum; Lawson-Williams, Makeba; Holland, Alexandria; Bello, Adebayo J.; Sexton, Darren W.; Olorunniji, Femi J.

doi:10.3390/ijms26020586

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Conditional Split Inteins: Adaptable Tools for Programming Protein Functions

by

Callum Shepherd

,

Makeba Lawson-Williams

,

Alexandria Holland

,

Adebayo J. Bello

,

Darren W. Sexton

and

Femi J. Olorunniji

^*

School of Pharmacy & Biomolecular Sciences, Faculty of Health, Innovation, Technology and Science, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, UK

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(2), 586; https://doi.org/10.3390/ijms26020586

Submission received: 2 December 2024 / Revised: 5 January 2025 / Accepted: 6 January 2025 / Published: 11 January 2025

(This article belongs to the Special Issue New Molecular Research and Perspective: Enzyme and Its Catalysis)

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Abstract

Split inteins are biological mechanisms for the operation of the spatiotemporal control of protein activities. They function through protein trans-splicing, in which their N- and C-terminal fragments are expressed contiguously with two protein halves. The subsequent self-excision upon recognition of the complimentary fragment yields a mature, complete, and functional protein. The conditional regulation of protein splicing through environmental factors or the attachment of regulatory modules can be used to determine when and where a protein will operate, providing potential novel approaches for engineering biology applications. This review will discuss current split intein applications and the mechanistic basis for novel species classification. These considerations can provide guidance in intein and extein engineering through activation strategies, in the design of spatial arrangements, and in taking advantage of unique reaction environments. This can pave the way for the future implementation of novel split intein discoveries and the selection of appropriate intein species and aid in designing novel protein engineering strategies.

Keywords: split inteins; conditionality; protein trans-splicing

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MDPI and ACS Style

Shepherd, C.; Lawson-Williams, M.; Holland, A.; Bello, A.J.; Sexton, D.W.; Olorunniji, F.J. Conditional Split Inteins: Adaptable Tools for Programming Protein Functions. Int. J. Mol. Sci. 2025, 26, 586. https://doi.org/10.3390/ijms26020586

AMA Style

Shepherd C, Lawson-Williams M, Holland A, Bello AJ, Sexton DW, Olorunniji FJ. Conditional Split Inteins: Adaptable Tools for Programming Protein Functions. International Journal of Molecular Sciences. 2025; 26(2):586. https://doi.org/10.3390/ijms26020586

Chicago/Turabian Style

Shepherd, Callum, Makeba Lawson-Williams, Alexandria Holland, Adebayo J. Bello, Darren W. Sexton, and Femi J. Olorunniji. 2025. "Conditional Split Inteins: Adaptable Tools for Programming Protein Functions" International Journal of Molecular Sciences 26, no. 2: 586. https://doi.org/10.3390/ijms26020586

APA Style

Shepherd, C., Lawson-Williams, M., Holland, A., Bello, A. J., Sexton, D. W., & Olorunniji, F. J. (2025). Conditional Split Inteins: Adaptable Tools for Programming Protein Functions. International Journal of Molecular Sciences, 26(2), 586. https://doi.org/10.3390/ijms26020586

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Conditional Split Inteins: Adaptable Tools for Programming Protein Functions

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