Antibacterial and anticancer activities of orphan biosynthetic gene clusters from Atlantis II Red Sea brine pool

Laila Ziko; Al-Hussein A Saqr; Amged Ouf; Matthias Gimpel; Ramy K Aziz; Peter Neubauer; Rania Siam

doi:10.1186/s12934-019-1103-3

Antibacterial and anticancer activities of orphan biosynthetic gene clusters from Atlantis II Red Sea brine pool

Microb Cell Fact. 2019 Mar 18;18(1):56. doi: 10.1186/s12934-019-1103-3.

Authors

Laila Ziko¹, Al-Hussein A Saqr², Amged Ouf^{1

2}, Matthias Gimpel³, Ramy K Aziz⁴, Peter Neubauer³, Rania Siam^{5

6}

Affiliations

¹ Graduate Program of Biotechnology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Cairo, 11835, Egypt.
² Department of Biology, School of Sciences and Engineering, The American University in Cairo, SSE (Parcel 7), Second Floor, Office: Room 2194, AUC Avenue, New Cairo, Cairo, 11835, Egypt.
³ Chair of Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, Ackerstrasse 76, ACK24, 13355, Berlin, Germany.
⁴ Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
⁵ Graduate Program of Biotechnology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Cairo, 11835, Egypt. rsiam@aucegypt.edu.
⁶ Department of Biology, School of Sciences and Engineering, The American University in Cairo, SSE (Parcel 7), Second Floor, Office: Room 2194, AUC Avenue, New Cairo, Cairo, 11835, Egypt. rsiam@aucegypt.edu.

Abstract

Background: Cancer and infectious diseases are problematic because of continuous emergence of drug resistance. One way to address this enormous global health threat is bioprospecting the unlikeliest environments, such as extreme marine niches, which have tremendous biodiversity that is barely explored. One such environment is the Red Sea brine pool, Atlantis II Deep (ATII). Here, we functionally screened a fosmid library of metagenomic DNA isolated from the ATII lower convective layer (LCL) for antibacterial and anticancer activities.

Results: Selected clones, 14-7E and 10-2G, displayed antibacterial effects on the marine strain Bacillus sp. Cc6. Moreover, whole cell lysates from 14-7E and 10-2G exhibited decreased cell viability against MCF-7 (39.1% ± 6.6, 42% ± 8.1 at 50% v/v) and U2OS cells (35.7% ± 1.9, 79.9% ± 5.9 at 50% v/v), respectively. By sequencing the insert DNA from 14-7E and 10-2G, we identified two putative orphan biosynthetic gene clusters. Both clusters harbored putative ATP-binding cassette (ABC) transporter permeases and S-adenosylmethionine-related genes. Interestingly, the biosynthetic gene cluster identified on 14-7E is of archaeal origin and harbors a putative transcription factor. Several identified genes may be responsible for the observed antibacterial and anticancer activities. The 14-7E biosynthetic gene cluster may be encoding enzymes producing a specialized metabolite (effect of detected genes involved in C-C bond formation and glycosylation). The bioactivity may also be due to predicted subtilases encoded by this cluster. The 10-2G cluster harbored putative glycosyltransferase and non-ribosomal peptide synthase genes; thus the observed activity of this clone could be caused by a bioactive peptide.

Conclusions: The ATII LCL prokaryotic metagenome hosts putative orphan biosynthetic gene clusters that confer antibiotic and anticancer effects. Further biochemical studies should characterize the detected bioactive components, and the potential use of 14-7E metabolite for antibiosis and 10-2G metabolite as a selective anti-breast cancer drug.

Keywords: Antibacterial; Anticancer; Atlantis II Red Sea brine pool; Orphan biosynthetic gene clusters; Specialized metabolism.

MeSH terms

Anti-Bacterial Agents
Antineoplastic Agents
Biodiversity
Cloning, Molecular / methods
Metagenome / genetics*
Multigene Family / genetics*
Seawater / microbiology*

Substances

Anti-Bacterial Agents
Antineoplastic Agents