Discovery of nostatin A, an azole-containing proteusin with
prominent cytostatic and pro-apoptotic activity

J 2025

Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity

DELAWSKA, Katerina; Jan HAJEK; Katerina VORACOVA; Marek KUZMA; Jan MARES et al.

Základní údaje

Originální název

Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity

Autoři

Vydání

ORGANIC & BIOMOLECULAR CHEMISTRY, CAMBRIDGE (ENGLAND), ROYAL SOC CHEMISTRY, 2025, 1477-0520

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10401 Organic chemistry

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.700 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90242/25:00140894

Organizační jednotka

CIISB III

Klíčová slova anglicky

NATURAL-PRODUCTS; CELL-CYCLE; BIOSYNTHESIS; STRATEGIES; INHIBITORS; MICROCINS; PEPTIDES; SPONGE

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 3. 2025 18:30, Mgr. Eva Dubská

Anotace

V originále

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium Nostoc sp. Its structure was established based on the core peptide sequence encoded in the biosynthetic gene cluster recovered from the producing strain and subsequent detailed nuclear magnetic resonance and high-resolution mass spectrometry analyses. NosA, composed of a 30 amino-acid peptide core, features a unique combination of moieties previously not reported in RiPPs: the simultaneous presence of oxazole/thiazole heterocycles, dehydrobutyrine/dehydroalanine residues, and a sactionine bond. NosA includes an isobutyl-modified proline residue, highly unusual in natural products. NosA inhibits proliferation of multiple cancer cell lines at low nanomolar concentration while showing no hemolysis. It induces cell cycle arrest in S-phase followed by mitochondrial apoptosis employing a mechanism different from known tubulin binding and DNA damaging compounds. NosA also inhibits Staphylococcus strains while it exhibits no effect in other tested bacteria or yeasts. Due to its novel structure and selective bioactivity, NosA represents an excellent candidate for combinatorial chemistry approaches leading to development of novel NosA-based lead compounds.

Návaznosti

90242, velká výzkumná infrastruktura

Název: CIISB III

Citovat

DELAWSKA, Katerina; Jan HAJEK; Katerina VORACOVA; Marek KUZMA; Jan MARES; Katerina VICKOVA; Alan KADEK; Dominika TUCKOVA; Filip GALLOB; Petra DIVOKA; Martin MOOS; Stanislav OPEKAR; Lukas KOCH; Kumar SAURAV; David SEDLAK; Petr NOVAK; Petra URAJOVA; Jason DEAN; Radek GAZAK; Timo J H NIEDERMEYER; Zdenek KAMENIK; Petr SIMEK; Andreas VILLUNGER a Pavel HROUZEK. Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity. ORGANIC & BIOMOLECULAR CHEMISTRY. CAMBRIDGE (ENGLAND): ROYAL SOC CHEMISTRY, 2025, roč. 23, č. 2, s. 449-460. ISSN 1477-0520. Dostupné z: https://doi.org/10.1039/d4ob01395f.

@article{2486882,
   author = {Delawska, Katerina and Hajek, Jan and Voracova, Katerina and Kuzma, Marek and Mares, Jan and Vickova, Katerina and Kadek, Alan and Tuckova, Dominika and Gallob, Filip and Divoka, Petra and Moos, Martin and Opekar, Stanislav and Koch, Lukas and Saurav, Kumar and Sedlak, David and Novak, Petr and Urajova, Petra and Dean, Jason and Gazak, Radek and Niedermeyer, Timo J H and Kamenik, Zdenek and Simek, Petr and Villunger, Andreas and Hrouzek, Pavel},
   article_location = {CAMBRIDGE (ENGLAND)},
   article_number = {2},
   doi = {https://doi.org/10.1039/d4ob01395f},
   keywords = {NATURAL-PRODUCTS; CELL-CYCLE; BIOSYNTHESIS; STRATEGIES; INHIBITORS; MICROCINS; PEPTIDES; SPONGE},
   language = {eng},
   issn = {1477-0520},
   journal = {ORGANIC & BIOMOLECULAR CHEMISTRY},
   title = {Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity},
   url = {https://pubs.rsc.org/en/content/articlelanding/2025/ob/d4ob01395f},
   volume = {23},
   year = {2025}
}

TY  - JOUR
ID  - 2486882
AU  - Delawska, Katerina - Hajek, Jan - Voracova, Katerina - Kuzma, Marek - Mares, Jan - Vickova, Katerina - Kadek, Alan - Tuckova, Dominika - Gallob, Filip - Divoka, Petra - Moos, Martin - Opekar, Stanislav - Koch, Lukas - Saurav, Kumar - Sedlak, David - Novak, Petr - Urajova, Petra - Dean, Jason - Gazak, Radek - Niedermeyer, Timo J H - Kamenik, Zdenek - Simek, Petr - Villunger, Andreas - Hrouzek, Pavel
PY  - 2025
TI  - Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity
JF  - ORGANIC & BIOMOLECULAR CHEMISTRY
VL  - 23
IS  - 2
SP  - 449-460
EP  - 449-460
PB  - ROYAL SOC CHEMISTRY
SN  - 14770520
KW  - NATURAL-PRODUCTS
KW  - CELL-CYCLE
KW  - BIOSYNTHESIS
KW  - STRATEGIES
KW  - INHIBITORS
KW  - MICROCINS
KW  - PEPTIDES
KW  - SPONGE
UR  - https://pubs.rsc.org/en/content/articlelanding/2025/ob/d4ob01395f
N2  - Ribosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium Nostoc sp. Its structure was established based on the core peptide sequence encoded in the biosynthetic gene cluster recovered from the producing strain and subsequent detailed nuclear magnetic resonance and high-resolution mass spectrometry analyses. NosA, composed of a 30 amino-acid peptide core, features a unique combination of moieties previously not reported in RiPPs: the simultaneous presence of oxazole/thiazole heterocycles, dehydrobutyrine/dehydroalanine residues, and a sactionine bond. NosA includes an isobutyl-modified proline residue, highly unusual in natural products. NosA inhibits proliferation of multiple cancer cell lines at low nanomolar concentration while showing no hemolysis. It induces cell cycle arrest in S-phase followed by mitochondrial apoptosis employing a mechanism different from known tubulin binding and DNA damaging compounds. NosA also inhibits Staphylococcus strains while it exhibits no effect in other tested bacteria or yeasts. Due to its novel structure and selective bioactivity, NosA represents an excellent candidate for combinatorial chemistry approaches leading to development of novel NosA-based lead compounds.
ER  -

DELAWSKA, Katerina; Jan HAJEK; Katerina VORACOVA; Marek KUZMA; Jan MARES; Katerina VICKOVA; Alan KADEK; Dominika TUCKOVA; Filip GALLOB; Petra DIVOKA; Martin MOOS; Stanislav OPEKAR; Lukas KOCH; Kumar SAURAV; David SEDLAK; Petr NOVAK; Petra URAJOVA; Jason DEAN; Radek GAZAK; Timo J H NIEDERMEYER; Zdenek KAMENIK; Petr SIMEK; Andreas VILLUNGER a Pavel HROUZEK. Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity. \textit{ORGANIC \&{}amp; BIOMOLECULAR CHEMISTRY}. CAMBRIDGE (ENGLAND): ROYAL SOC CHEMISTRY, 2025, roč.~23, č.~2, s.~449-460. ISSN~1477-0520. Dostupné z: https://doi.org/10.1039/d4ob01395f.

Přehled o publikaci