Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products

Louise Kjaerulff; Asfandyar Sikandar; Nestor Zaburannyi; Sebastian Adam; Jennifer Herrmann; Jesko Koehnke; Rolf Müller

doi:10.1021/acschembio.7b00676

Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products

Louise Kjaerulff, Asfandyar Sikandar, Nestor Zaburannyi, Sebastian Adam, Jennifer Herrmann, Jesko Koehnke, Rolf Müller^*

^*Corresponding author for this work

32 Citations (Scopus)

Abstract

Thioviridamide is a structurally unique ribosomally synthesized and post-translationally modified peptide that contains several thioamide bonds and is active against a number of cancer cell lines. In the search for naturally occurring thioviridamide analogs, we employed genome mining that led to the identification of several related gene clusters. Chemical screening followed by cultivation and isolation yielded thioholgamides A and B, two new additions to the thioviridamide family with several amino acid substitutions, a different N-capping moiety, and with one less thioamide bond. Thioholgamides display improved cytotoxicity in the submicromolar range against a range of cell lines and an IC₅₀ of 30 nM for thioholgamide A against HCT-116 cells. Herein, we report the isolation and structural elucidation of thioholgamides A and B, a proposed biosynthetic cluster for their production, and their bioactivities against a larger panel of microorganisms and cancer cell lines.

Original language	English
Journal	ACS chemical biology
Volume	12
Issue number	11
Pages (from-to)	2837-2841
Number of pages	5
ISSN	1554-8929
DOIs	https://doi.org/10.1021/acschembio.7b00676
Publication status	Published - 2017
Externally published	Yes

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10.1021/acschembio.7b00676

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title = "Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products",

abstract = "Thioviridamide is a structurally unique ribosomally synthesized and post-translationally modified peptide that contains several thioamide bonds and is active against a number of cancer cell lines. In the search for naturally occurring thioviridamide analogs, we employed genome mining that led to the identification of several related gene clusters. Chemical screening followed by cultivation and isolation yielded thioholgamides A and B, two new additions to the thioviridamide family with several amino acid substitutions, a different N-capping moiety, and with one less thioamide bond. Thioholgamides display improved cytotoxicity in the submicromolar range against a range of cell lines and an IC50 of 30 nM for thioholgamide A against HCT-116 cells. Herein, we report the isolation and structural elucidation of thioholgamides A and B, a proposed biosynthetic cluster for their production, and their bioactivities against a larger panel of microorganisms and cancer cell lines.",

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doi = "10.1021/acschembio.7b00676",

language = "English",

volume = "12",

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T1 - Thioholgamides

T2 - Thioamide-Containing Cytotoxic RiPP Natural Products

AU - Kjaerulff, Louise

AU - Sikandar, Asfandyar

AU - Zaburannyi, Nestor

AU - Adam, Sebastian

AU - Herrmann, Jennifer

AU - Koehnke, Jesko

AU - Müller, Rolf

PY - 2017

Y1 - 2017

N2 - Thioviridamide is a structurally unique ribosomally synthesized and post-translationally modified peptide that contains several thioamide bonds and is active against a number of cancer cell lines. In the search for naturally occurring thioviridamide analogs, we employed genome mining that led to the identification of several related gene clusters. Chemical screening followed by cultivation and isolation yielded thioholgamides A and B, two new additions to the thioviridamide family with several amino acid substitutions, a different N-capping moiety, and with one less thioamide bond. Thioholgamides display improved cytotoxicity in the submicromolar range against a range of cell lines and an IC50 of 30 nM for thioholgamide A against HCT-116 cells. Herein, we report the isolation and structural elucidation of thioholgamides A and B, a proposed biosynthetic cluster for their production, and their bioactivities against a larger panel of microorganisms and cancer cell lines.

AB - Thioviridamide is a structurally unique ribosomally synthesized and post-translationally modified peptide that contains several thioamide bonds and is active against a number of cancer cell lines. In the search for naturally occurring thioviridamide analogs, we employed genome mining that led to the identification of several related gene clusters. Chemical screening followed by cultivation and isolation yielded thioholgamides A and B, two new additions to the thioviridamide family with several amino acid substitutions, a different N-capping moiety, and with one less thioamide bond. Thioholgamides display improved cytotoxicity in the submicromolar range against a range of cell lines and an IC50 of 30 nM for thioholgamide A against HCT-116 cells. Herein, we report the isolation and structural elucidation of thioholgamides A and B, a proposed biosynthetic cluster for their production, and their bioactivities against a larger panel of microorganisms and cancer cell lines.

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DO - 10.1021/acschembio.7b00676

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JO - A C S Chemical Biology

JF - A C S Chemical Biology

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ER -

Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products

Abstract

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