Development of novel reactions for amide bond formation and creation of peptide-like functional materials

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K14495
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biofunction/Bioprocess
• Research Institution: Waseda University
• Principal Investigator: Kino Kuniki 早稲田大学, 理工学術院, 教授 (60318764)
• Research Collaborator: HARA Ryotaro ; Suzuki Shin
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: アミド化合物 / アミド結合形成反応 / ペプチド / アデニル化酵素 / 求核置換反応 / ポリリン酸キナーゼ / D-アミノ酸 / バイオプロセス

Outline of Final Research Achievements

Amide compounds are useful materials as bio-functional molecules and chemicals. We have developed a unique method for amino acid amide synthesis using adenylation domain (A-domain) of nonribosomal peptide synthetase. In this method, A-domain adenylates carboxy group of amino acid and followed by nucleophilic acyl substitution reaction with amine. In this research, novel methods of synthesizing various amide compounds using adenylation enzymes were developed.
Fatty acid amides were synthesized by a fatty acyl-AMP ligase which can adenylate various length of fatty acids. Aryl carboxylic acid amides were synthesized by DhbE which can adenylate benzoic acid and 14 kinds of monosubstituted benzoic acids. D-Amino acid-containing dipeptides were synthesized by A-domain (TycA-A) which can adenylate some D-amino acids. On the other hand, the ATP regeneration system from AMP was developed using class III polyphosphate kinase 2 and was coupled with L-Trp-L-Pro synthesis using TycA-A.

Free Research Field

応用生物化学