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The application of the bacterial cytosine deaminase (bCD)\/5\u2010fluorocytosine (5\u2010FC) approach has been beneficial and progressive within the current field of cancer therapy because of the enhanced bystander effect. The basis of this method is the preferential deamination of 5\u2010FC to 5\u2010fluorouracil by cancer cells expressing cytosine deaminase (CD), which strongly inhibits DNA synthesis and RNA function, effectively targeting tumor cells. However, the poor binding affinity of toward 5\u2010FC compared to the natural substrate cytosine and\/or inappropriate thermostability limits the clinical applications of this gene therapy approach. Nowadays, many genetic engineering studies have been carried out to solve and improve the activity of this enzyme. In the current review, we intend to discuss the biotechnological aspects of <jats:italic>Escherichia coli<\/jats:italic> CD, including its structure, functions, molecular cloning, and protein engineering. We will also explore its relevance in cancer clinical trials. By examining these aspects, we hope to provide a thorough understanding of <jats:italic>E. coli<\/jats:italic> CD and its potential applications in cancer therapy.<\/jats:p>","DOI":"10.1002\/bab.2516","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T03:59:52Z","timestamp":1695614392000},"page":"5-16","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Escherichia coli <i>cytosine deaminase: Structural and biotechnological aspects<\/i>"],"prefix":"10.1002","volume":"71","author":[{"given":"Parisa","family":"Vosough","sequence":"first","affiliation":[{"name":"Student Research Committee Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies Shiraz University of Medical Sciences  Shiraz 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