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Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies

Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies

Nguyen, Van Duy, Nguyen, Thanh Tra, Pham, Thu Thuy, Packianather, Michael and Le, Chi Hieu ORCID: 0000-0002-5168-2297 (2019) Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies. International Microbiology. pp. 1-13. ISSN 1139-6709 (Print), 1618-1905 (Online) (doi:https://doi.org/10.1007/s10123-019-00070-8)

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Abstract

Azurin, a bacteriocin produced by a human gut bacterium Pseudomonas aeruginosa, can reveal selectively cytotoxic and induceapoptosis in cancer cells. After overcoming two phase I trials, a functional region of Azurin called p28 has been approved as adrug for the treatment of brain tumor glioma by FDA. The present study aims to improve a screening procedure and assessgenetic diversity of Azurin genes in P. aeruginosa and Azurin-like genes in the gut microbiome of a specific population inVietnam and global populations. Firstly, both cultivation-dependent and cultivation-independent techniques based on genomicand metagenomic DNAs extracted from fecal samples of the healthy specific population were performed and optimized to detectAzurin genes. Secondly, the Azurin gene sequences were analyzed and compared with global populations by using bioinfor-matics tools. Finally, the screening procedure improved from the first step was applied for screening Azurin-like genes, followedby the protein synthesis and NCI in vitro screening for anticancer activity. As a result, this study has successfully optimized theannealing temperatures to amplify DNAs for screening Azurin genes and applying to Azurin-like genes from human gutmicrobiota. The novelty of this study is the first of its kind to classify Azurin genes into five different genotypes at a globalscale and confirm the potential anticancer activity of three Azurin-like synthetic proteins (Cnazu1, Dlazu11, and Ruazu12). Theresults contribute to the procedure development applied for screening anticancer proteins from human microbiome and acomprehensive understanding of their therapeutic response at a genetic level.

Item Type: Article
Additional Information: This paper is one of the R&D outputs of the following externally-funded project: "Innovative design and development of anticancer bacteriocins from the human microbiome: The Big-Data and Bioinformatics approach", funded by NAFOSTED & NEWTON FUND (09/017 – 03/2018). Budget: 7,100 GBP.
Uncontrolled Keywords: Anticancer proteins, Azurin, Cancer therapy, Genetic diversity, Microbiome, NCI in vitro screening
Subjects: T Technology > TA Engineering (General). Civil engineering (General)
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Engineering Science
Last Modified: 19 May 2019 22:58
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: GREAT 3
URI: http://gala.gre.ac.uk/id/eprint/23457

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