Structural and functional analysis of ATP-dependent ligases in macrolactam biosynthesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25850050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied microbiology
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: MIYANAGA Akimasa 東京工業大学, 理工学研究科, 助教 (10623126)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 生合成 / マクロラクタム抗生物質 / β-アミノ酸 / ATP依存型リガーゼ / X線結晶構造解析 / ポリケチド

Outline of Final Research Achievements

Macrolactam antibiotics such as vicenistatin and cremimycin contain various beta-amino acids at the starter position of the polyketide backbone. In their biosynthesis, a standalone ATP-dependent ligase serves as a gatekeeper for a specific beta-amino acid recognition and activation. However, the beta-amino acid recognition mechanism of ATP-dependent ligases remains elusive. To elucidate the beta-amino acid recognition mechanism, we carried out the structural and mutational studies of the ATP-dependent ligases including VinN, which activates 3-methylaspartate in vicenistatin biosynthesis and CmiS6, which activates 3-aminononanoate in cremimycin biosynthesis. The VinN structure complexed with 3-methylaspartate provides detail mechanistic insights into the selective recognition of beta-amino acids in this family of enzymes. We also identified the biosynthetic gene cluster of hitachimycin, which is another macrolactam compound.

Free Research Field

農学