Open Access

Journal of the American Chemical Society, volume 139, issue 27, pages 9203-9212

Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens

Xu Fei ¹

Nazari Behnam ¹

Moon Kyuho ¹

Bushin Leah B ¹

Seyedsayamdost Mohammad R ^{1, 2}

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Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States |

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, United States |

Publication type: Journal Article

Publication date: 2017-06-29

American Chemical Society (ACS)

Journal: Journal of the American Chemical Society

Quartile SCImago

Quartile WOS

Impact factor: 15

ISSN: 00027863, 15205126

DOI: 10.1021/jacs.7b02716

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PubMed ID: 28590725

General Chemistry

Catalysis

Biochemistry

Colloid and Surface Chemistry

Abstract

An important unresolved issue in microbial secondary metabolite production is the abundance of biosynthetic gene clusters that are not expressed under typical laboratory growth conditions. These so-called silent or cryptic gene clusters are sources of new natural products, but how they are silenced, and how they may be rationally activated are areas of ongoing investigation. We recently devised a chemogenetic high-throughput screening approach ("HiTES") to discover small molecule elicitors of silent biosynthetic gene clusters. This method was successfully applied to a Gram-negative bacterium; it has yet to be implemented in the prolific antibiotic-producing streptomycetes. Herein we have developed a high-throughput transcriptional assay format in Streptomyces spp. by leveraging eGFP, inserted both at a neutral site and inside the biosynthetic cluster of interest, as a read-out for secondary metabolite synthesis. Using this approach, we successfully used HiTES to activate a silent gene cluster in Streptomyces albus J1074. Our results revealed the cytotoxins etoposide and ivermectin as potent inducers, allowing us to isolate and structurally characterize 14 novel small molecule products of the chosen cluster. One of these molecules is a novel antifungal, while several others inhibit a cysteine protease implicated in cancer. Studies addressing the mechanism of induction by the two elicitors led to the identification of a pathway-specific transcriptional repressor that silences the gene cluster under standard growth conditions. The successful application of HiTES will allow future interrogations of the biological regulation and chemical output of the countless silent gene clusters in Streptomyces spp.

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Citations by journals

	1 2 3 4 5
Frontiers in Microbiology	Frontiers in Microbiology, 5, 4.27% Frontiers in Microbiology 5 publications, 4.27%
Microorganisms	Microorganisms, 5, 4.27% Microorganisms 5 publications, 4.27%
Current Opinion in Microbiology	Current Opinion in Microbiology, 5, 4.27% Current Opinion in Microbiology 5 publications, 4.27%
Angewandte Chemie - International Edition	Angewandte Chemie - International Edition, 5, 4.27% Angewandte Chemie - International Edition 5 publications, 4.27%
Angewandte Chemie	Angewandte Chemie, 5, 4.27% Angewandte Chemie 5 publications, 4.27%
Journal of Industrial Microbiology and Biotechnology	Journal of Industrial Microbiology and Biotechnology, 5, 4.27% Journal of Industrial Microbiology and Biotechnology 5 publications, 4.27%
ACS Chemical Biology	ACS Chemical Biology, 4, 3.42% ACS Chemical Biology 4 publications, 3.42%
Antibiotics	Antibiotics, 3, 2.56% Antibiotics 3 publications, 2.56%
Natural Product Reports	Natural Product Reports, 3, 2.56% Natural Product Reports 3 publications, 2.56%
Nucleic Acids Research	Nucleic Acids Research, 3, 2.56% Nucleic Acids Research 3 publications, 2.56%
mBio	mBio, 3, 2.56% mBio 3 publications, 2.56%
RSC Advances	RSC Advances, 2, 1.71% RSC Advances 2 publications, 1.71%
Molecules	Molecules, 2, 1.71% Molecules 2 publications, 1.71%
Marine Drugs	Marine Drugs, 2, 1.71% Marine Drugs 2 publications, 1.71%
Communications Chemistry	Communications Chemistry, 2, 1.71% Communications Chemistry 2 publications, 1.71%
Applied and Environmental Microbiology	Applied and Environmental Microbiology, 2, 1.71% Applied and Environmental Microbiology 2 publications, 1.71%
BioMed Research International	BioMed Research International, 1, 0.85% BioMed Research International 1 publication, 0.85%
Biotechnology and Bioengineering	Biotechnology and Bioengineering, 1, 0.85% Biotechnology and Bioengineering 1 publication, 0.85%
International Journal of Systematic and Evolutionary Microbiology	International Journal of Systematic and Evolutionary Microbiology, 1, 0.85% International Journal of Systematic and Evolutionary Microbiology 1 publication, 0.85%
Chemical and Pharmaceutical Bulletin	Chemical and Pharmaceutical Bulletin, 1, 0.85% Chemical and Pharmaceutical Bulletin 1 publication, 0.85%
Metabolites	Metabolites, 1, 0.85% Metabolites 1 publication, 0.85%
Biomolecules	Biomolecules, 1, 0.85% Biomolecules 1 publication, 0.85%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 0.85% International Journal of Molecular Sciences 1 publication, 0.85%
Frontiers in Pharmacology	Frontiers in Pharmacology, 1, 0.85% Frontiers in Pharmacology 1 publication, 0.85%
Frontiers in Plant Science	Frontiers in Plant Science, 1, 0.85% Frontiers in Plant Science 1 publication, 0.85%
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry	Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 1, 0.85% Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 1 publication, 0.85%
Fermentation	Fermentation, 1, 0.85% Fermentation 1 publication, 0.85%
Scientific Reports	Scientific Reports, 1, 0.85% Scientific Reports 1 publication, 0.85%
Nature Communications	Nature Communications, 1, 0.85% Nature Communications 1 publication, 0.85%
	1 2 3 4 5

Citations by publishers

	2 4 6 8 10 12 14 16 18
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 18, 15.38% Multidisciplinary Digital Publishing Institute (MDPI) 18 publications, 15.38%
Springer Nature	Springer Nature, 18, 15.38% Springer Nature 18 publications, 15.38%
Wiley	Wiley, 16, 13.68% Wiley 16 publications, 13.68%
Elsevier	Elsevier, 12, 10.26% Elsevier 12 publications, 10.26%
Frontiers Media S.A.	Frontiers Media S.A., 7, 5.98% Frontiers Media S.A. 7 publications, 5.98%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 6, 5.13% Royal Society of Chemistry (RSC) 6 publications, 5.13%
American Society for Microbiology	American Society for Microbiology, 6, 5.13% American Society for Microbiology 6 publications, 5.13%
American Chemical Society (ACS)	American Chemical Society (ACS), 5, 4.27% American Chemical Society (ACS) 5 publications, 4.27%
Taylor & Francis	Taylor & Francis, 4, 3.42% Taylor & Francis 4 publications, 3.42%
Oxford University Press	Oxford University Press, 3, 2.56% Oxford University Press 3 publications, 2.56%
Hindawi Limited	Hindawi Limited, 1, 0.85% Hindawi Limited 1 publication, 0.85%
Microbiology Society	Microbiology Society, 1, 0.85% Microbiology Society 1 publication, 0.85%
Pharmaceutical Society of Japan	Pharmaceutical Society of Japan, 1, 0.85% Pharmaceutical Society of Japan 1 publication, 0.85%
Society of Synthetic Organic Chemistry	Society of Synthetic Organic Chemistry, 1, 0.85% Society of Synthetic Organic Chemistry 1 publication, 0.85%
KeAi Communications Co.	KeAi Communications Co., 1, 0.85% KeAi Communications Co. 1 publication, 0.85%
Pleiades Publishing	Pleiades Publishing, 1, 0.85% Pleiades Publishing 1 publication, 0.85%
Polskie Towarzystwo Mikrobiologow/Polish Society of Microbiologists	Polskie Towarzystwo Mikrobiologow/Polish Society of Microbiologists, 1, 0.85% Polskie Towarzystwo Mikrobiologow/Polish Society of Microbiologists 1 publication, 0.85%
eLife Sciences Publications	eLife Sciences Publications, 1, 0.85% eLife Sciences Publications 1 publication, 0.85%
Annual Reviews	Annual Reviews, 1, 0.85% Annual Reviews 1 publication, 0.85%
Instituto de Tecnologia do Parana	Instituto de Tecnologia do Parana, 1, 0.85% Instituto de Tecnologia do Parana 1 publication, 0.85%
Bentham Science	Bentham Science, 1, 0.85% Bentham Science 1 publication, 0.85%
	2 4 6 8 10 12 14 16 18

We do not take into account publications that without a DOI.
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Xu F. et al. Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens // Journal of the American Chemical Society. 2017. Vol. 139. No. 27. pp. 9203-9212.

GOST all authors (up to 50) Copy

Xu F., Nazari B., Moon K., Bushin L. B., Seyedsayamdost M. R. Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens // Journal of the American Chemical Society. 2017. Vol. 139. No. 27. pp. 9203-9212.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1021/jacs.7b02716

UR - https://doi.org/10.1021%2Fjacs.7b02716

TI - Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens

T2 - Journal of the American Chemical Society

AU - Moon, Kyuho

AU - Bushin, Leah B

AU - Seyedsayamdost, Mohammad R

AU - Xu, Fei

AU - Nazari, Behnam

PY - 2017

DA - 2017/06/29 00:00:00

PB - American Chemical Society (ACS)

SP - 9203-9212

IS - 27

VL - 139

PMID - 28590725

SN - 0002-7863

SN - 1520-5126

ER -

BibTex |

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BibTex Copy

@article{2017_Xu,

author = {Kyuho Moon and Leah B Bushin and Mohammad R Seyedsayamdost and Fei Xu and Behnam Nazari},

title = {Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens},

journal = {Journal of the American Chemical Society},

year = {2017},

volume = {139},

publisher = {American Chemical Society (ACS)},

month = {jun},

url = {https://doi.org/10.1021%2Fjacs.7b02716},

number = {27},

pages = {9203--9212},

doi = {10.1021/jacs.7b02716}

}

MLA

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MLA Copy

Xu, Fei, et al. “Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens.” Journal of the American Chemical Society, vol. 139, no. 27, Jun. 2017, pp. 9203-9212. https://doi.org/10.1021%2Fjacs.7b02716.

Found error?

Publisher

American Chemical Society (ACS)

Journal

Journal of the American Chemical Society

Quartile SCImago

Quartile WOS

Impact factor

ISSN

00027863 (Print)
15205126 (Electronic)