Sammanfattning

Prenylation is a common step in the biosynthesis of many natural products and plays an important role in increasing their structural diversity and enhancing biological activity. Muscoride A is a linear peptide alkaloid that contain two contiguous oxazoles and unusual prenyl groups that protect the amino- and carboxy-termini. Here we identified the 12.7 kb muscoride (mus) biosynthetic gene clusters from Nostoc spp. PCC 7906 and UHCC 0398. The mus biosynthetic gene clusters encode enzymes for the heterocyclization, oxidation, and prenylation of the MusE precursor protein. The mus biosynthetic gene clusters encode two copies of the cyanobactin prenyltransferase, MusF1 and MusF2. The predicted tetrapeptide substrate of MusF1 and MusF2 was synthesized through a novel tandem cyclization route in only eight steps. Biochemical assays demonstrated that MusF1 acts on the carboxy-terminus while MusF2 acts on the amino-terminus of the tetrapeptide substrate. We show that the MusF2 enzyme catalyzes the reverse or forward prenylation of amino-termini from Nostoc spp. PCC 7906 and UHCC 0398, respectively. This finding expands the regiospecific chemical functionality of cyanobactin prenyltransferases and the chemical diversity of the cyanobactin family of natural products to include bis-prenylated polyoxazole linear peptides.
Originalspråkengelska
TidskriftACS Chemical Biology
Volym14
Utgåva12
Sidor (från-till)2683-2690
Antal sidor8
ISSN1554-8929
DOI
StatusPublicerad - 20 dec 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi

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Mattila, Antti ; Andsten, Rose-Marie ; Jumppanen, Mikael ; Assante, Michele ; Jokela, Jouni ; Wahlsten, Matti ; Mikula, Kornelia M ; Sigindere, Cihad ; Kwak, Daniel H. ; Gugger, Muriel ; Koskela, Harri ; Sivonen, Kaarina ; Liu, Xinyu ; Yli-Kauhaluoma, Jari ; Iwaï, Hideo ; Fewer, David. / Biosynthesis of the bis-prenylated alkaloids muscoride A and B. I: ACS Chemical Biology. 2019 ; Vol. 14, Nr. 12. s. 2683-2690.
@article{0f38200b3c4b497baa7332330932d200,
title = "Biosynthesis of the bis-prenylated alkaloids muscoride A and B",
abstract = "Prenylation is a common step in the biosynthesis of many natural products and plays an important role in increasing their structural diversity and enhancing biological activity. Muscoride A is a linear peptide alkaloid that contain two contiguous oxazoles and unusual prenyl groups that protect the amino- and carboxy-termini. Here we identified the 12.7 kb muscoride (mus) biosynthetic gene clusters from Nostoc spp. PCC 7906 and UHCC 0398. The mus biosynthetic gene clusters encode enzymes for the heterocyclization, oxidation, and prenylation of the MusE precursor protein. The mus biosynthetic gene clusters encode two copies of the cyanobactin prenyltransferase, MusF1 and MusF2. The predicted tetrapeptide substrate of MusF1 and MusF2 was synthesized through a novel tandem cyclization route in only eight steps. Biochemical assays demonstrated that MusF1 acts on the carboxy-terminus while MusF2 acts on the amino-terminus of the tetrapeptide substrate. We show that the MusF2 enzyme catalyzes the reverse or forward prenylation of amino-termini from Nostoc spp. PCC 7906 and UHCC 0398, respectively. This finding expands the regiospecific chemical functionality of cyanobactin prenyltransferases and the chemical diversity of the cyanobactin family of natural products to include bis-prenylated polyoxazole linear peptides.",
keywords = "1182 Biochemistry, cell and molecular biology, AROMATIC PRENYLTRANSFERASES, CYANOBACTIN, PEPTIDES, FAMILY",
author = "Antti Mattila and Rose-Marie Andsten and Mikael Jumppanen and Michele Assante and Jouni Jokela and Matti Wahlsten and Mikula, {Kornelia M} and Cihad Sigindere and Kwak, {Daniel H.} and Muriel Gugger and Harri Koskela and Kaarina Sivonen and Xinyu Liu and Jari Yli-Kauhaluoma and Hideo Iwa{\"i} and David Fewer",
year = "2019",
month = "12",
day = "20",
doi = "10.1021/acschembio.9b00620",
language = "English",
volume = "14",
pages = "2683--2690",
journal = "ACS Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "12",

}

Biosynthesis of the bis-prenylated alkaloids muscoride A and B. / Mattila, Antti; Andsten, Rose-Marie; Jumppanen, Mikael; Assante, Michele; Jokela, Jouni; Wahlsten, Matti; Mikula, Kornelia M; Sigindere, Cihad; Kwak, Daniel H.; Gugger, Muriel; Koskela, Harri; Sivonen, Kaarina; Liu, Xinyu; Yli-Kauhaluoma, Jari; Iwaï, Hideo; Fewer, David.

I: ACS Chemical Biology, Vol. 14, Nr. 12, 20.12.2019, s. 2683-2690.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Biosynthesis of the bis-prenylated alkaloids muscoride A and B

AU - Mattila, Antti

AU - Andsten, Rose-Marie

AU - Jumppanen, Mikael

AU - Assante, Michele

AU - Jokela, Jouni

AU - Wahlsten, Matti

AU - Mikula, Kornelia M

AU - Sigindere, Cihad

AU - Kwak, Daniel H.

AU - Gugger, Muriel

AU - Koskela, Harri

AU - Sivonen, Kaarina

AU - Liu, Xinyu

AU - Yli-Kauhaluoma, Jari

AU - Iwaï, Hideo

AU - Fewer, David

PY - 2019/12/20

Y1 - 2019/12/20

N2 - Prenylation is a common step in the biosynthesis of many natural products and plays an important role in increasing their structural diversity and enhancing biological activity. Muscoride A is a linear peptide alkaloid that contain two contiguous oxazoles and unusual prenyl groups that protect the amino- and carboxy-termini. Here we identified the 12.7 kb muscoride (mus) biosynthetic gene clusters from Nostoc spp. PCC 7906 and UHCC 0398. The mus biosynthetic gene clusters encode enzymes for the heterocyclization, oxidation, and prenylation of the MusE precursor protein. The mus biosynthetic gene clusters encode two copies of the cyanobactin prenyltransferase, MusF1 and MusF2. The predicted tetrapeptide substrate of MusF1 and MusF2 was synthesized through a novel tandem cyclization route in only eight steps. Biochemical assays demonstrated that MusF1 acts on the carboxy-terminus while MusF2 acts on the amino-terminus of the tetrapeptide substrate. We show that the MusF2 enzyme catalyzes the reverse or forward prenylation of amino-termini from Nostoc spp. PCC 7906 and UHCC 0398, respectively. This finding expands the regiospecific chemical functionality of cyanobactin prenyltransferases and the chemical diversity of the cyanobactin family of natural products to include bis-prenylated polyoxazole linear peptides.

AB - Prenylation is a common step in the biosynthesis of many natural products and plays an important role in increasing their structural diversity and enhancing biological activity. Muscoride A is a linear peptide alkaloid that contain two contiguous oxazoles and unusual prenyl groups that protect the amino- and carboxy-termini. Here we identified the 12.7 kb muscoride (mus) biosynthetic gene clusters from Nostoc spp. PCC 7906 and UHCC 0398. The mus biosynthetic gene clusters encode enzymes for the heterocyclization, oxidation, and prenylation of the MusE precursor protein. The mus biosynthetic gene clusters encode two copies of the cyanobactin prenyltransferase, MusF1 and MusF2. The predicted tetrapeptide substrate of MusF1 and MusF2 was synthesized through a novel tandem cyclization route in only eight steps. Biochemical assays demonstrated that MusF1 acts on the carboxy-terminus while MusF2 acts on the amino-terminus of the tetrapeptide substrate. We show that the MusF2 enzyme catalyzes the reverse or forward prenylation of amino-termini from Nostoc spp. PCC 7906 and UHCC 0398, respectively. This finding expands the regiospecific chemical functionality of cyanobactin prenyltransferases and the chemical diversity of the cyanobactin family of natural products to include bis-prenylated polyoxazole linear peptides.

KW - 1182 Biochemistry, cell and molecular biology

KW - AROMATIC PRENYLTRANSFERASES

KW - CYANOBACTIN

KW - PEPTIDES

KW - FAMILY

U2 - 10.1021/acschembio.9b00620

DO - 10.1021/acschembio.9b00620

M3 - Article

VL - 14

SP - 2683

EP - 2690

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 12

ER -