開催日: 2017/09/20 - 2017/09/22
Amino-group carrier protein (AmCP) is involved in the biosynthesis of non-proteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), a key building block for a novel di-peptide compound, vazabitide A. We screened 848 actinomycetes strains using polymerase chain reaction to investigate the diversity of this newly identified biosynthetic machinery mediated by AmCP. Successive draft genome sequencing of positive strains revealed twelve putative gene clusters containing AmCP genes. Among them, the heterologous expression of a putative gene cluster from Streptomyces sp. SoC090715LN-17 led to the discovery of a novel natural product, s56-p1 that possesses a unique hydrazone unit attached to a DADH-derived amino acid. This result shows the structural diversity of natural products biosynthesized via AmCP-mediated machinery and paves the way for investigation of untapped AmCP-containing gene clusters distributed among actinomycetes. Further, in vivo and in vitro characterization of enzymes encoded in the gene cluster for s56-p1 revealed the biosynthetic pathway for hydrazineacetic acid (HAA), a putative precursor of the unique hydrazone unit of s56-p1. This finding would give insight into the mechanism of a nitrogen-nitrogen covalent bond formation in natural products biosynthesis.