Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp

doi:10.3390/antibiotics11111631

. 2022 Nov 15;11(11):1631.

doi: 10.3390/antibiotics11111631.

Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp

Affiliations

¹ Department of Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo 11837, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62764, Egypt.
³ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
⁴ Department of Biology, University of Iowa, Iowa City, IA 52242-1324, USA.
⁵ Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt.
⁶ Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, 52074 Aachen, Germany.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁹ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.
¹⁰ Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
¹¹ Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt.

PMID: 36421275
PMCID: PMC9686727
DOI: 10.3390/antibiotics11111631

Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp

Noha M Gamaleldin et al. Antibiotics (Basel). 2022.

. 2022 Nov 15;11(11):1631.

doi: 10.3390/antibiotics11111631.

Authors

Affiliations

¹ Department of Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo 11837, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62764, Egypt.
³ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
⁴ Department of Biology, University of Iowa, Iowa City, IA 52242-1324, USA.
⁵ Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt.
⁶ Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, 52074 Aachen, Germany.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁹ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.
¹⁰ Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
¹¹ Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt.

PMID: 36421275
PMCID: PMC9686727
DOI: 10.3390/antibiotics11111631

Abstract

Malaria is a persistent illness with a great public health concern. To combat this fatal disease, developing effective antimalarial medications has become a necessity. In the present study, we described the actinomycetes associated with the Red Sea soft coral Nephthea sp. and isolated a strain that was sub-cultured in three different media (M1, ISP2, and OLIGO). Actinomycete isolate's phylogenetic analysis of the 16S rRNA gene revealed that it belongs to the genus Rhodococcus. In vitro screening of the antimalarial activity for three extracts against Plasmodium falciparum was carried out. Non-targeted metabolomics for the chemical characterization of the isolated actinomycete species UA111 derived extracts were employed using high-resolution liquid chromatography-mass spectrometry (LC-HR-MS) for dereplication purposes. Additionally, statistical analysis of the vast LC-MS data was performed using MetaboAnalyst 5.0. Finally, an in silico analysis was conducted to investigate the potential chemical compounds that could be the source of the antimalarial potential. The results revealed that ISP2 media extract is the most effective against Plasmodium falciparum, according to antimalarial screening (IC₅₀ 8.5 µg/mL), in contrast, OLIGO media extract was inactive. LC-HRMS-based metabolomics identified a range of metabolites, mainly alkaloids, from the genus Rhodococcus. On the other hand, multivariate analysis showed chemical diversity between the analyzed samples, with ISP2 extract being optimal. The docking analysis was able to anticipate the various patterns of interaction of the annotated compounds with three malarial protein targets (P. falciparum kinase, P. falciparum cytochrome bc1 complex, and P. falciparum lysyl-tRNA synthetase). Among all of the test compounds, perlolyrine (11) and 3097-B2 (12) displayed the best docking profiles. In conclusion, this work demonstrated the value of the established method for the metabolic profiling of marine actinomycetes using the data from liquid chromatography-mass spectrometry (LC-MS), which helps to streamline the difficult isolation stages required for their chemical characterization. In addition, the antimalarial efficacy of this strain has intriguing implications for future pharmaceutical development.

Keywords: PCA; PLS-DA; Rhodococcus; actinomycetes; antimalarial; metabolomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Phylogenetic tree of the 16S rRNA gene-marking *Rhodococcus* sp. UR111 isolate and its closest relatives.

**Figure 2**
Metabolites dereplicated from *Rhodococcus* sp. crude extract.

**Figure 3**
Metabolomics multivariate analysis. (A) PCA pairwise score plot of the unsupervised method; (B) 2D PCA scores plot of the unsupervised method; (C) 2D PCA loadings plot of the unsupervised method; (D) Heatmap plot.

**Figure 4**
Metabolomics multivariate analysis. (A) PLS pairwise score plot; (B) 2D PCA scores plot of the unsupervised method; (C) 2D PCA loadings plot of the unsupervised method; (D) Heatmap plot.

**Figure 5**
Presumptive mode of interaction of molecules 11 and 12 within active site of *P. falciparum* kinase (PDB ID: 1V0P); (A) Perlolyrine (11); (B) 3097-B2 (12).

**Figure 6**
Presumptive mode of interaction of molecule 11 (A) and 12 (B) within active site of *P. falciparum* mitochondrial cytochrome bc1 complex (PDB ID: 4PD4). showing H-bond in blue and/or green arrows and solvent accessible contour as black-dotted line around whole molecule.

**Figure 7**
Presumptive mode of interaction of molecules 11, 12, and 9X0 within active site of *P. falciparum* lysyl-tRNA synthetase (PfKRS1; PDB ID: 6AGT). (A) Perlolyrine (11); (B) 3097-B2 (12).

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References

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1. Abdelmohsen U.R., Yang C., Horn H., Hajjar D., Ravasi T., Hentschel U. Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity. Mar. Drugs. 2014;12:2771–2789. doi: 10.3390/md12052771. - DOI - PMC - PubMed
1. Elsayed Y., Fahim J., Abdelmohsen U., Fouad M. Chemical and Biological Investigation of the Marine Bacterium Rhodococcus Sp. UA13. J. Adv. Biomed. Pharm. Sci. 2021;4:1–6. doi: 10.21608/jabps.2020.38170.1094. - DOI
1. Bell K.S., Philp J.C., Aw D.W.J., Christofi N. A Review: The Genus Rhodococcus. J. Appl. Microbiol. 1998;85:195–210. doi: 10.1046/j.1365-2672.1998.00525.x. - DOI - PubMed
1. Elsayed Y., Refaat J., Yasmin Elsayed C., Abdelmohsen U.R., Fouad M.A. The Genus Rhodococcus as a Source of Novel Bioactive Substances: A Review. J. Pharmacogn. Phytochem. 2017;6:83–92.

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[1] Elsayed Y., Refaat J., Abdelmohsen U.R., Othman E.M., Stopper H., Fouad M.A. Metabolomic Profiling and Biological Investigation of the Marine Sponge-Derived Bacterium Rhodococcus sp. UA13. Phytochem. Anal. 2018;29:543–548. doi: 10.1002/pca.2765. - DOI - PubMed

[2] Elsayed Y., Refaat J., Abdelmohsen U.R., Othman E.M., Stopper H., Fouad M.A. Metabolomic Profiling and Biological Investigation of the Marine Sponge-Derived Bacterium Rhodococcus sp. UA13. Phytochem. Anal. 2018;29:543–548. doi: 10.1002/pca.2765. - DOI - PubMed

[3] Abdelmohsen U.R., Yang C., Horn H., Hajjar D., Ravasi T., Hentschel U. Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity. Mar. Drugs. 2014;12:2771–2789. doi: 10.3390/md12052771. - DOI - PMC - PubMed

[4] Abdelmohsen U.R., Yang C., Horn H., Hajjar D., Ravasi T., Hentschel U. Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity. Mar. Drugs. 2014;12:2771–2789. doi: 10.3390/md12052771. - DOI - PMC - PubMed

[5] Elsayed Y., Fahim J., Abdelmohsen U., Fouad M. Chemical and Biological Investigation of the Marine Bacterium Rhodococcus Sp. UA13. J. Adv. Biomed. Pharm. Sci. 2021;4:1–6. doi: 10.21608/jabps.2020.38170.1094. - DOI

[6] Elsayed Y., Fahim J., Abdelmohsen U., Fouad M. Chemical and Biological Investigation of the Marine Bacterium Rhodococcus Sp. UA13. J. Adv. Biomed. Pharm. Sci. 2021;4:1–6. doi: 10.21608/jabps.2020.38170.1094. - DOI

[7] Bell K.S., Philp J.C., Aw D.W.J., Christofi N. A Review: The Genus Rhodococcus. J. Appl. Microbiol. 1998;85:195–210. doi: 10.1046/j.1365-2672.1998.00525.x. - DOI - PubMed

[8] Bell K.S., Philp J.C., Aw D.W.J., Christofi N. A Review: The Genus Rhodococcus. J. Appl. Microbiol. 1998;85:195–210. doi: 10.1046/j.1365-2672.1998.00525.x. - DOI - PubMed

[9] Elsayed Y., Refaat J., Yasmin Elsayed C., Abdelmohsen U.R., Fouad M.A. The Genus Rhodococcus as a Source of Novel Bioactive Substances: A Review. J. Pharmacogn. Phytochem. 2017;6:83–92.

[10] Elsayed Y., Refaat J., Yasmin Elsayed C., Abdelmohsen U.R., Fouad M.A. The Genus Rhodococcus as a Source of Novel Bioactive Substances: A Review. J. Pharmacogn. Phytochem. 2017;6:83–92.

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Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp

Affiliations

Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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