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

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

doi:10.1186/s12934-019-1103-3

Abstract

BackgroundCancer 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.ResultsSelected 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.ConclusionsThe 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.

Highlights

Cancer and infectious diseases are problematic because of continuous emergence of drug resist‐ ance
Mining nature for bioactive molecules has proven valuable in investigating diverse environmental niches, and will undoubtedly shed light on new chemistries with bioactivity, antibiosis and anticancer effects [3,4,5]
The diameters were measured from a single dish containing 96 clones (Additional file 1: Figure S1)

Summary

Introduction

Cancer and infectious diseases are problematic because of continuous emergence of drug resist‐ ance. 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). Since the early forties some antibiotic compounds have been known to possess anticancer activity [6]. This group of anticancer antibiotics includes drugs of diverse chemical structures, such as bleomycin, actinomycin D and doxorubicin [6, 7]

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