Structural and functional analysis of vicenistatin biosynthetic enzymes for elucidating the construction mechanism of β-amino acid starter unit

Miyanaga Akimasa, Shinohara Yuji, Iwasawa Syohei, Cieslak Jolanta, Kudo Fumitaka, Eguchi Tadashi

doi:10.24496/tennenyuki.57.0_oral33

<p> Macrolactam natural products such as vicenistatin, cremimycin, and incednine are an important class of macrocyclic polyketides, and many of them contain various b-amino acids at the starter position of polyketide backbone. Among those, vicenistatin is produced by Streptomyces halstedii HC34, and possesses a unique b-amino acid unit, 3-aminoisobutyrate (3-AIB), at the starter position of polyketide backbone. In this study, we carried out the structural and mutational studies of vicenistatin biosynthetic enzymes to understand the structural basis of the construction mechanism of b-amino acid starter unit. First, we determined the crystal structure of adenylation enzyme VinN, which transfers 3-methylaspartate onto standalone acyl carrier protein (ACP) VinL and plays a crucial role in the selection of b-amino acid starter unit for polyketide synthase in the vicenistatin biosynthesis. The visualization of the interaction of VinN with 3-methylaspartate allowed the elucidation of b-amino acid recognition mechanism. Next, we determined the crystal structure of acyltransferase VinK, which transfers 3-AIB-containting dipeptide group from VinL to the ACP domain of VinP1 polyketide synthase. Consequently, mechanistic insights into the recognition of substrates dipeptide and ACP were revealed. We also determined the crystal structure of amidohydrolase VinJ, which catalyzes the removal of alanyl group from polyketide chain. The crystal structure of VinJ shows that VinJ has a unique hydrophobic polyketide binding tunnel. In this presentation, the details of their substrate recognition mechanisms will be discussed.</p>

Structural and functional analysis of vicenistatin biosynthetic enzymes for elucidating the construction mechanism of β-amino acid starter unit

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