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Biosynthesis of β-Amino Acid-Containing Macrolactam Polyketides

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Abstract

β-Amino acid-containing macrolactam antibiotics are an important class of macrocyclic polyketides in Actinobacteria. These macrolactam antibiotics are biosynthesized from various β-amino acid starter units, contributing to their structural diversity. In this chapter, the biosynthetic mechanisms of these β-amino acid-containing macrolactam polyketides are summarized. Conserved biosynthetic machinery is used to incorporate a β-amino acid starter unit into the polyketide skeleton. The VinN-type adenylation enzyme loads a specific β-amino acid unit onto an acyl carrier protein, and the VinM-type adenylation enzyme aminoacylates the β-amino acid moiety to form a dipeptidyl unit, which is subsequently loaded onto polyketide synthases for polyketide chain elongation. A terminal aminoacyl moiety on biosynthetic intermediates is a characteristic feature in the biosynthesis of β-amino acid-containing macrolactam polyketides. Structural analysis of key biosynthetic enzymes has revealed the basis of selective recognition of β-amino acids and dipeptidyl moieties of polyketide intermediates. Biosynthetic engineering strategies have enabled the production of macrolactam polyketide derivatives in which a β-amino acid substrate analog is incorporated.

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  1. Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo, 113-8657, Japan

    Akimasa Miyanaga

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    Hayato Ishikawa

  2. Chiba University, Chiba, Japan

    Hiromitsu Takayama

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Miyanaga, A. (2023). Biosynthesis of β-Amino Acid-Containing Macrolactam Polyketides. In: Ishikawa, H., Takayama, H. (eds) New Tide of Natural Product Chemistry. Springer, Singapore. https://doi.org/10.1007/978-981-99-1714-3_8

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