Informations et ressources scientifiques
sur le développement des zones arides et semi-arides

Accueil du site → Doctorat → Egypte → Mining for specialized metabolism genes in Red Sea brine pool prokaryotic metagenomes for antibacterial and anticancer activities

American University in Cairo (2019)

Mining for specialized metabolism genes in Red Sea brine pool prokaryotic metagenomes for antibacterial and anticancer activities

Ziko, Laila

Titre : Mining for specialized metabolism genes in Red Sea brine pool prokaryotic metagenomes for antibacterial and anticancer activities

Auteur : Ziko, Laila

Université de soutenance : American University in Cairo

Grade : Doctor of Philosophy (PhD) 2019

Résumé partiel
Antibiotic and anticancer drug resistance are current global health threats, thus new antibiotics and anticancer agents are required to treat the strains and cancers that are currently untreatable with the available drug spectrum. One way to search for new chemotherapeutics is to search nature, particularly metagenomes of un-cultured microbial communities. A subset of specialized metabolites (SMs) produced by microbes confer activities of pharmaceutical importance, such as antibacterial and anticancer effects, and are coded by specialized metabolism gene clusters (SMGCs) in the organisms’ genomes. We aimed to search for SMGCs in the metagenomes of Red Sea brine microbial communities by employing computational methods and functional screening methods. Metagenome mining was performed for shotgun metagenomic sequences from Atlantis II (ATII), Discovery Deep (DD), Kebrit Deep (KD) brine water and ATII, DD and Non-brine (NB) sediment samples of assembled metagenomic prokaryotic environmental DNA. SMGCs were detected by using the antibiotics and secondary metabolite analysis shell (antiSMASH) tool. A total of 2,751 SMGCs were detected, which belonged to 28 different SM classes. The SMGCs were thoroughly analysed for promising potential antibacterial and anticancer activity, taxonomic evaluation for all the sites was performed, and chemical structure prediction was also performed. The potential biotechnological applications of the detected Red Sea brine SMGCs was studied, as well as the potential role of the detected SMGCs in microbe-environment interactions, extremophile survival and microbial diversity in extreme environments. As a preliminary proof of concept, a detected polyketide synthase type III (PKSIII) enzyme was expressed. Functional screening was employed to detect antibacterial and anticancer activities from the Atlantis II Lower Convective Layer (ATII LCL) metagenomic fosmid library comprising 10,656 clones. A phenotypic assay was employed to detect clones of antibacterial effect against a marine Bacillus strain (Bacillus Cc6), yielding 11 positive clones.

Mots clés : Specialized Metabolism, Red Sea, brine, metagenomics

Présentation

Page publiée le 22 décembre 2020