Biosynthesis of the bis-prenylated alkaloids muscoride A and B

Antti Mattila, Rose-Marie Andsten, Mikael Jumppanen, Michele Assante, Jouni Jokela, Matti Wahlsten, Kornelia M Mikula, Cihad Sigindere, Daniel H. Kwak, Muriel Gugger, Harri Koskela, Kaarina Sivonen, Xinyu Liu, Jari Yli-Kauhaluoma, Hideo Iwaï, David Fewer

Research output: Contribution to journalArticleScientificpeer-review


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.
Original languageEnglish
JournalACS Chemical Biology
Issue number12
Pages (from-to)2683-2690
Number of pages8
Publication statusPublished - 20 Dec 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology

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