Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking

To discover novel antimalarial and anticancer compounds, we carried out a genome analysis, bioassay, metabolite profiling, and molecular docking of marine sediment actinobacteria strain GMY01. The whole-genome sequence analysis revealed that <i>Streptomyces</i> sp. GMY01 (7.9 Mbp) is mos...

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Main Authors: Jaka Widada, Ema Damayanti, Mustofa Mustofa, Achmad Dinoto, Rifki Febriansah, Triana Hertiani
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/11/8/1930
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author Jaka Widada
Ema Damayanti
Mustofa Mustofa
Achmad Dinoto
Rifki Febriansah
Triana Hertiani
author_facet Jaka Widada
Ema Damayanti
Mustofa Mustofa
Achmad Dinoto
Rifki Febriansah
Triana Hertiani
author_sort Jaka Widada
collection DOAJ
description To discover novel antimalarial and anticancer compounds, we carried out a genome analysis, bioassay, metabolite profiling, and molecular docking of marine sediment actinobacteria strain GMY01. The whole-genome sequence analysis revealed that <i>Streptomyces</i> sp. GMY01 (7.9 Mbp) is most similar to <i>Streptomyces sennicomposti</i> strain RCPT1-4<sup>T</sup> with an average nucleotide identity (ANI) and ANI based on BLAST+ (ANIb) values of 98.09 and 97.33% (>95%). An in vitro bioassay of the GMY01 bioactive on <i>Plasmodium falciparum</i> FCR3, cervical carcinoma of HeLa cell and lung carcinoma of HTB cells exhibited moderate activity (IC<sub>50</sub> value of 46.06; 27.31 and 33.75 µg/mL) with low toxicity on Vero cells as a normal cell (IC<sub>50</sub> value of 823.3 µg/mL). Metabolite profiling by LC-MS/MS analysis revealed that the active fraction of GMY01 contained carbohydrate-based compounds, C17H29NO14 (471.15880 Da) as a major compound (97.50%) and mannotriose (C18H32O16; 504.16903 Da, 1.96%) as a minor compound. Molecular docking analysis showed that mannotriose has a binding affinity on glutathione reductase (GR) and glutathione-S-transferase (GST) of <i>P. falciparum</i> and on autophagy proteins (mTORC1 and mTORC2) of cancer cells. <i>Streptomyces sennicomposti</i> GMY01 is a potential bacterium producing carbohydrate-based bioactive compounds with anti-plasmodial and anticancer activities and with low toxicity to normal cells.
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spelling doaj.art-825f751f90584d3787c16b16387319b02023-11-19T02:16:17ZengMDPI AGMicroorganisms2076-26072023-07-01118193010.3390/microorganisms11081930Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular DockingJaka Widada0Ema Damayanti1Mustofa Mustofa2Achmad Dinoto3Rifki Febriansah4Triana Hertiani5Department of Agricultural Microbiology, Faculty of Agriculture, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaResearch Center for Food Technology and Processing, National Research and Innovation Agency (BRIN), Gunungkidul 55861, IndonesiaDepartment of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gajah Mada, Yogyakarta 55281, IndonesiaResearch Center for Applied Microbiology, National Research and Innovation Agency (BRIN), Cibinong 16911, IndonesiaFaculty of Medicine and Health Sciences, Universitas Muhammadiyah, Yogyakarta 55183, IndonesiaFaculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaTo discover novel antimalarial and anticancer compounds, we carried out a genome analysis, bioassay, metabolite profiling, and molecular docking of marine sediment actinobacteria strain GMY01. The whole-genome sequence analysis revealed that <i>Streptomyces</i> sp. GMY01 (7.9 Mbp) is most similar to <i>Streptomyces sennicomposti</i> strain RCPT1-4<sup>T</sup> with an average nucleotide identity (ANI) and ANI based on BLAST+ (ANIb) values of 98.09 and 97.33% (>95%). An in vitro bioassay of the GMY01 bioactive on <i>Plasmodium falciparum</i> FCR3, cervical carcinoma of HeLa cell and lung carcinoma of HTB cells exhibited moderate activity (IC<sub>50</sub> value of 46.06; 27.31 and 33.75 µg/mL) with low toxicity on Vero cells as a normal cell (IC<sub>50</sub> value of 823.3 µg/mL). Metabolite profiling by LC-MS/MS analysis revealed that the active fraction of GMY01 contained carbohydrate-based compounds, C17H29NO14 (471.15880 Da) as a major compound (97.50%) and mannotriose (C18H32O16; 504.16903 Da, 1.96%) as a minor compound. Molecular docking analysis showed that mannotriose has a binding affinity on glutathione reductase (GR) and glutathione-S-transferase (GST) of <i>P. falciparum</i> and on autophagy proteins (mTORC1 and mTORC2) of cancer cells. <i>Streptomyces sennicomposti</i> GMY01 is a potential bacterium producing carbohydrate-based bioactive compounds with anti-plasmodial and anticancer activities and with low toxicity to normal cells.https://www.mdpi.com/2076-2607/11/8/1930anticancerantimalariaactinobacteriagenome miningmolecular dockingmetabolomic
spellingShingle Jaka Widada
Ema Damayanti
Mustofa Mustofa
Achmad Dinoto
Rifki Febriansah
Triana Hertiani
Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking
Microorganisms
anticancer
antimalaria
actinobacteria
genome mining
molecular docking
metabolomic
title Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking
title_full Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking
title_fullStr Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking
title_full_unstemmed Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking
title_short Marine-Derived <i>Streptomyces sennicomposti</i> GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking
title_sort marine derived i streptomyces sennicomposti i gmy01 with anti plasmodial and anticancer activities genome analysis in vitro bioassay metabolite profiling and molecular docking
topic anticancer
antimalaria
actinobacteria
genome mining
molecular docking
metabolomic
url https://www.mdpi.com/2076-2607/11/8/1930
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