2. Academic Validation
  3. Identification of the Fluvirucin B2 (Sch 38518) Biosynthetic Gene Cluster from Actinomadura fulva subsp. indica ATCC 53714: substrate Specificity of the β-Amino Acid Selective Adenylating Enzyme FlvN

Identification of the Fluvirucin B2 (Sch 38518) Biosynthetic Gene Cluster from Actinomadura fulva subsp. indica ATCC 53714: substrate Specificity of the β-Amino Acid Selective Adenylating Enzyme FlvN

  • Biosci Biotechnol Biochem. 2016 May;80(5):935-41. doi: 10.1080/09168451.2015.1132155.
Akimasa Miyanaga 1,  Yuki Hayakawa 2,  Mario Numakura 1,  Junko Hashimoto 3,  Kuniko Teruya 4,  Takashi Hirano 4 5,  Kazuo Shin-Ya 6,  Fumitaka Kudo 1,  Tadashi Eguchi 2
Affiliations

Affiliations

  • 1 a Department of Chemistry , Tokyo Institute of Technology , Tokyo , Japan.
  • 2 b Department of Chemistry and Materials Science , Tokyo Institute of Technology , Tokyo , Japan.
  • 3 c Japan Biological Informatics Consortium , Tokyo , Japan.
  • 4 d Okinawa Biotechnology Business Support Center , Okinawa Institute of Advanced Sciences , Uruma , Japan.
  • 5 e Okinawa Biotechnology Business Support Center , Okinawa Science and Technology Promotion Center , Uruma , Japan.
  • 6 f National Institute of Advanced Industrial Science and Technology , Tokyo , Japan.
PMID: 26818633 DOI: 10.1080/09168451.2015.1132155
Abstract

Fluvirucins are 14-membered macrolactam polyketides that show Antifungal and antivirus activities. Fluvirucins have the β-alanine starter unit at their polyketide skeletons. To understand the construction mechanism of the β-alanine moiety in fluvirucin biosyntheses, we have identified the biosynthetic cluster of fluvirucin B2 produced from Actinomadura fulva subsp. indica ATCC 53714. The identified gene cluster contains three polyketide synthases, four characteristic β-amino acid-carrying Enzymes, one decarboxylase, and one amidohydrolase. We next investigated the activity of the adenylation enzyme FlvN, which is a key enzyme for the selective incorporation of a β-amino acid substrate. FlvN showed strong preference for l-aspartate over other Amino acids such as β-alanine. Based on these results, we propose a biosynthetic pathway for fluvirucin B2.

Keywords

adenylation enzyme; fluvirucin; genome mining; macrolactam antibiotics; polyketide.

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