S40 Lactam-forming amide ligase found in the streptothricin biosynthetic enzymes
Monday, July 21, 2014: 4:00 PM
Regency Ballroom EF, Second Floor (St. Louis Hyatt Regency at the Arch)
Yoshimitsu Hamano, Department of Bioscience, Fukui Prefectural University, Fukui, Japan
Streptothricins (STs; syn. nourseothricins, racemomycins, and yazumycins), which inhibit protein biosynthesis in prokaryotic cells, and strongly inhibit the growth of eukaryotes, are a group of N-glycoside toxic antibiotics. The first member of this group, ST-F, was isolated by Waksman from Streptomyces lavendulae in 1943. All ST-related compounds consist of a carbamoylated D-gulosamine to which the (3S)-3,6-diaminohexanoic acid (L-β-lysine) oligopeptide (one to seven residues) and the amide form of the unusual amino acid streptolidine (streptolidine lactam) are attached. Recently, we reported the identification of three NRPSs involved in the biosynthesis of diverse L-β-lysine oligopeptides in the STs (Nat. Chem. Biol., 8, 791-797, 2012).

Amide ligase, which is also known as L-amino acid ligase, belongs to the ATP-dependent (ADP-forming) carboxylate-amine/thiol ligase superfamily that contains glutathione synthetase and D-alanine-D-alanine ligase. In this group, ATP and Mg2+ are generally required for peptide synthesis, and aminoacyl phosphate is synthesized as the reaction intermediate. In addition to NRPSs, amide ligases are also known to participate in the biosynthesis of peptide natural products.

In this presentation, an amide ligase catalyzing intramolecular lactamization in the streptolidine lactam biosynthesis will be discussed. In addition, the unique biosynthetic pathway for the substrate of this enzyme will be presented.