Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.

Strain NJES-13 T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-de...

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Published in:Marine Drugs
Main Authors: Wen-Zhuo Zhu, Shu-Heng Wang, Hui-Min Gao, Ya-Ming Ge, Jun Dai, Xiao-Ling Zhang, Qiao Yang
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2021
Subjects:
Online Access:https://doi.org/10.3390/md20010034
https://doaj.org/article/41bfb472db514ea09316e91bc0b7a602
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spelling ftdoajarticles:oai:doaj.org/article:41bfb472db514ea09316e91bc0b7a602 2023-05-15T13:45:15+02:00 Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov. Wen-Zhuo Zhu Shu-Heng Wang Hui-Min Gao Ya-Ming Ge Jun Dai Xiao-Ling Zhang Qiao Yang 2021-12-01T00:00:00Z https://doi.org/10.3390/md20010034 https://doaj.org/article/41bfb472db514ea09316e91bc0b7a602 EN eng MDPI AG https://www.mdpi.com/1660-3397/20/1/34 https://doaj.org/toc/1660-3397 doi:10.3390/md20010034 1660-3397 https://doaj.org/article/41bfb472db514ea09316e91bc0b7a602 Marine Drugs, Vol 20, Iss 34, p 34 (2021) gut microbiota Gephyromycinifex aptenodytis angucycline/angucyclinone derivatives exopolysaccharides type III PKS biogenetic pathway Biology (General) QH301-705.5 article 2021 ftdoajarticles https://doi.org/10.3390/md20010034 2022-12-30T22:03:28Z Strain NJES-13 T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-derived exopolysaccharides (EPSs). Moreover, it produced bioactive angucycline/angucyclinone derivatives (ADs) and contained one type III polyketide synthase (T3PKS), thus demonstrating great potential to produce novel bioactive compounds. However, the low productivity of the potential new AD metabolite was the main obstacle for its chemical structure elucidation. In this study, to increase the concentration of targeted metabolites, the influence of cellular morphology on AD metabolism in strain NJES-13 T was determined using glass bead-enhanced fermentation. Based on the cellular ultra-structural observation driven by bacterial EPSs, and quantitative analysis of the targeted metabolites, the successful increasing of the productivity of three AD metabolites was achieved. Afterward, a new frigocyclinone analogue was isolated and then identified as 2-hydroxy-frigocyclinone, as well as two other known ADs named 2-hydroxy-tetrangomycin (2-HT) and gephyromycin (GPM). Three AD metabolites were found to demonstrate different bioactivities. Both C-2 hydroxyl substitutes, 2-hydroxy-tetrangomycin and 2-hydroxy-frigocyclinone, exhibited variable inhibitory activities against Staphylococcus aureus , Bacillus subtilis and Candida albicans . Moreover, the newly identified 2-hydroxy-frigocyclinone also showed significant cytotoxicity against three tested human-derived cancerous cell lines (HL-60, Bel-7402 and A549), with all obtained IC 50 values less than 10 µM. Based on the genetic analysis after genomic mining, the plausible biogenetic pathway of the three bioactive ADs in strain NJES-13 T was also proposed. Article in Journal/Newspaper Antarc* Antarctic Directory of Open Access Journals: DOAJ Articles Antarctic The Antarctic Marine Drugs 20 1 34
institution Open Polar
collection Directory of Open Access Journals: DOAJ Articles
op_collection_id ftdoajarticles
language English
topic gut microbiota
Gephyromycinifex aptenodytis
angucycline/angucyclinone derivatives
exopolysaccharides
type III PKS
biogenetic pathway
Biology (General)
QH301-705.5
spellingShingle gut microbiota
Gephyromycinifex aptenodytis
angucycline/angucyclinone derivatives
exopolysaccharides
type III PKS
biogenetic pathway
Biology (General)
QH301-705.5
Wen-Zhuo Zhu
Shu-Heng Wang
Hui-Min Gao
Ya-Ming Ge
Jun Dai
Xiao-Ling Zhang
Qiao Yang
Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.
topic_facet gut microbiota
Gephyromycinifex aptenodytis
angucycline/angucyclinone derivatives
exopolysaccharides
type III PKS
biogenetic pathway
Biology (General)
QH301-705.5
description Strain NJES-13 T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-derived exopolysaccharides (EPSs). Moreover, it produced bioactive angucycline/angucyclinone derivatives (ADs) and contained one type III polyketide synthase (T3PKS), thus demonstrating great potential to produce novel bioactive compounds. However, the low productivity of the potential new AD metabolite was the main obstacle for its chemical structure elucidation. In this study, to increase the concentration of targeted metabolites, the influence of cellular morphology on AD metabolism in strain NJES-13 T was determined using glass bead-enhanced fermentation. Based on the cellular ultra-structural observation driven by bacterial EPSs, and quantitative analysis of the targeted metabolites, the successful increasing of the productivity of three AD metabolites was achieved. Afterward, a new frigocyclinone analogue was isolated and then identified as 2-hydroxy-frigocyclinone, as well as two other known ADs named 2-hydroxy-tetrangomycin (2-HT) and gephyromycin (GPM). Three AD metabolites were found to demonstrate different bioactivities. Both C-2 hydroxyl substitutes, 2-hydroxy-tetrangomycin and 2-hydroxy-frigocyclinone, exhibited variable inhibitory activities against Staphylococcus aureus , Bacillus subtilis and Candida albicans . Moreover, the newly identified 2-hydroxy-frigocyclinone also showed significant cytotoxicity against three tested human-derived cancerous cell lines (HL-60, Bel-7402 and A549), with all obtained IC 50 values less than 10 µM. Based on the genetic analysis after genomic mining, the plausible biogenetic pathway of the three bioactive ADs in strain NJES-13 T was also proposed.
format Article in Journal/Newspaper
author Wen-Zhuo Zhu
Shu-Heng Wang
Hui-Min Gao
Ya-Ming Ge
Jun Dai
Xiao-Ling Zhang
Qiao Yang
author_facet Wen-Zhuo Zhu
Shu-Heng Wang
Hui-Min Gao
Ya-Ming Ge
Jun Dai
Xiao-Ling Zhang
Qiao Yang
author_sort Wen-Zhuo Zhu
title Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.
title_short Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.
title_full Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.
title_fullStr Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.
title_full_unstemmed Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.
title_sort characterization of bioactivities and biosynthesis of angucycline/angucyclinone derivatives derived from gephyromycinifex aptenodytis gen. nov., sp. nov.
publisher MDPI AG
publishDate 2021
url https://doi.org/10.3390/md20010034
https://doaj.org/article/41bfb472db514ea09316e91bc0b7a602
geographic Antarctic
The Antarctic
geographic_facet Antarctic
The Antarctic
genre Antarc*
Antarctic
genre_facet Antarc*
Antarctic
op_source Marine Drugs, Vol 20, Iss 34, p 34 (2021)
op_relation https://www.mdpi.com/1660-3397/20/1/34
https://doaj.org/toc/1660-3397
doi:10.3390/md20010034
1660-3397
https://doaj.org/article/41bfb472db514ea09316e91bc0b7a602
op_doi https://doi.org/10.3390/md20010034
container_title Marine Drugs
container_volume 20
container_issue 1
container_start_page 34
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