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 af dette arbejde

32 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	ACS chemical biology
Vol/bind	12
Udgave nummer	11
Sider (fra-til)	2837-2841
Antal sider	5
ISSN	1554-8929
DOI	https://doi.org/10.1021/acschembio.7b00676
Status	Udgivet - 2017
Udgivet eksternt	Ja

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10.1021/acschembio.7b00676

Citationsformater

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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.",

author = "Louise Kjaerulff and Asfandyar Sikandar and Nestor Zaburannyi and Sebastian Adam and Jennifer Herrmann and Jesko Koehnke and Rolf M{\"u}ller",

year = "2017",

doi = "10.1021/acschembio.7b00676",

language = "English",

volume = "12",

pages = "2837--2841",

journal = "ACS chemical biology",

issn = "1554-8929",

publisher = "American Chemical Society",

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TY - JOUR

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.

U2 - 10.1021/acschembio.7b00676

DO - 10.1021/acschembio.7b00676

M3 - Journal article

C2 - 28981254

AN - SCOPUS:85034651970

SN - 1554-8929

VL - 12

SP - 2837

EP - 2841

JO - ACS chemical biology

JF - ACS chemical biology

IS - 11

ER -

Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products

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