Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59

A new approach to activate silent gene clusters for dormant secondary metabolite production has been developed by introducing gentamicin-resistance to an originally inactive, marine-derived fungal strain Penicillium purpurogenum G59. Upon treatment of the G59 spores with a high concentration of gent...

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Main Authors:	Chai, Yun-Jing, Cui, Cheng-Bin, Li, Chang-Wei, Wu, Chang-Jing, Tian, Cong-Kui, Hua, Wei
Format:	Online
Language:	English
Published:	MDPI 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347015/

id	pubmed-3347015
recordtype	oai_dc
spelling	pubmed-33470152012-05-18 Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59 Chai, Yun-Jing Cui, Cheng-Bin Li, Chang-Wei Wu, Chang-Jing Tian, Cong-Kui Hua, Wei Article A new approach to activate silent gene clusters for dormant secondary metabolite production has been developed by introducing gentamicin-resistance to an originally inactive, marine-derived fungal strain Penicillium purpurogenum G59. Upon treatment of the G59 spores with a high concentration of gentamicin in aqueous DMSO, a total of 181 mutants were obtained by single colony isolation. In contrast to the strain G59, the EtOAc extracts of nine mutant cultures showed inhibitory effects on K562 cells, indicating that the nine mutants had acquired capability to produce antitumor metabolites. This was evidenced by TLC and HPLC analysis of EtOAc extracts of G59 and the nine mutants. Further isolation and characterization demonstrated that four antitumor secondary metabolites, janthinone (1), fructigenine A (2), aspterric acid methyl ester (3) and citrinin (4), were newly produced by mutant 5-1-4 compared to the parent strain G59, and which were also not found in the secondary metabolites of other Penicillium purpurogenum strains. However, Compounds 1–4 inhibited the proliferation of K562 cells with inhibition rates of 34.6% (1), 60.8% (2), 31.7% (3) and 67.1% (4) at 100 μg/mL, respectively. The present study demonstrated the effectiveness of a simple, yet practical approach to activate the production of dormant fungal secondary metabolites by introducing acquired resistance to aminoglycoside antibiotics, which could be applied to the studies for eliciting dormant metabolic potential of fungi to obtain cryptic secondary metabolites. MDPI 2012-03-02 /pmc/articles/PMC3347015/ /pubmed/22611354 http://dx.doi.org/10.3390/md10030559 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chai, Yun-Jing Cui, Cheng-Bin Li, Chang-Wei Wu, Chang-Jing Tian, Cong-Kui Hua, Wei
spellingShingle	Chai, Yun-Jing Cui, Cheng-Bin Li, Chang-Wei Wu, Chang-Jing Tian, Cong-Kui Hua, Wei Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59
author_facet	Chai, Yun-Jing Cui, Cheng-Bin Li, Chang-Wei Wu, Chang-Jing Tian, Cong-Kui Hua, Wei
author_sort	Chai, Yun-Jing
title	Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59
title_short	Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59
title_full	Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59
title_fullStr	Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59
title_full_unstemmed	Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59
title_sort	activation of the dormant secondary metabolite production by introducing gentamicin-resistance in a marine-derived penicillium purpurogenum g59
description	A new approach to activate silent gene clusters for dormant secondary metabolite production has been developed by introducing gentamicin-resistance to an originally inactive, marine-derived fungal strain Penicillium purpurogenum G59. Upon treatment of the G59 spores with a high concentration of gentamicin in aqueous DMSO, a total of 181 mutants were obtained by single colony isolation. In contrast to the strain G59, the EtOAc extracts of nine mutant cultures showed inhibitory effects on K562 cells, indicating that the nine mutants had acquired capability to produce antitumor metabolites. This was evidenced by TLC and HPLC analysis of EtOAc extracts of G59 and the nine mutants. Further isolation and characterization demonstrated that four antitumor secondary metabolites, janthinone (1), fructigenine A (2), aspterric acid methyl ester (3) and citrinin (4), were newly produced by mutant 5-1-4 compared to the parent strain G59, and which were also not found in the secondary metabolites of other Penicillium purpurogenum strains. However, Compounds 1–4 inhibited the proliferation of K562 cells with inhibition rates of 34.6% (1), 60.8% (2), 31.7% (3) and 67.1% (4) at 100 μg/mL, respectively. The present study demonstrated the effectiveness of a simple, yet practical approach to activate the production of dormant fungal secondary metabolites by introducing acquired resistance to aminoglycoside antibiotics, which could be applied to the studies for eliciting dormant metabolic potential of fungi to obtain cryptic secondary metabolites.
publisher	MDPI
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347015/
_version_	1611528070434390016

Activation of the Dormant Secondary Metabolite Production by Introducing Gentamicin-Resistance in a Marine-Derived Penicillium purpurogenum G59

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