Gene involved in synthesis of cyclic peptide compound, method for producing cyclic peptide compound using the same, and transformant comprising the same

A method for producing a cyclic peptide compound, the method comprising:

• a step of culturing a transformant transformed with a gene, wherein the gene is involved in the production of the cyclic peptide compound in the transformant;
• and
• a step of collecting the cyclic peptide compound from the cultured transformant and/or culture solution,
• wherein the gene encodes a nonribosomal peptide synthetase (NRPS) having nonribosomal peptide synthase activity comprising, successively from the N terminus, the modules described below:
• a first module comprising successively from the N terminus a first adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 1 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 1 and a first peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 2 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 2;
• a second module comprising successively from the N terminus a first condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 3 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 3, a second adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 4 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 4, and a second peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 5 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 5;
• a third module comprising successively from the N terminus a second condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 6 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 6, a third adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 7 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 7, a first N-methyl transferase domain comprising the amino acid sequence as shown in SEQ ID NO:
• 8 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 8, and a third peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 9 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 9;
• a fourth module comprising successively from the N terminus a third condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 10 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 10, a fourth adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 11 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 11, and a fourth peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 12 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 12;
• a fifth module comprising successively from the N terminus a fourth condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 13 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 13, a fifth adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 14 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 14, a second N-methyl transferase domain comprising the amino acid sequence as shown in SEQ ID NO:
• 15 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 15, and a fifth peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 16 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 16;
• a sixth module comprising successively from the N terminus a fifth condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 17 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 17, a sixth adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 18 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 18, a third N-methyl transferase domain comprising the amino acid sequence as shown in SEQ ID NO:
• 19 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 19, and a sixth peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 20 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 20;
• a seventh module comprising successively from the N terminus a sixth condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 21 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 21, a seventh adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 22 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 22, a fourth N-methyl transferase domain comprising the amino acid sequence as shown in SEQ ID NO:
• 23 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 23, and a seventh peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 24 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 24;
• an eighth module comprising successively from the N terminus a seventh condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 25 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 25, an eighth adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 26 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 26, and an eighth peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 27 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 27;
• a ninth module comprising successively from the N terminus an eighth condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 28 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 28, a ninth adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 29 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 29, a fifth N-methyl transferase domain comprising the amino acid sequence as shown in SEQ ID NO:
• 30 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 30, and a ninth peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 31 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 31;
• and
• a tenth module comprising successively from the N terminus a ninth condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 32 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 32, a tenth adenylation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 33 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 33, a tenth peptidyl carrier protein domain comprising the amino acid sequence as shown in SEQ ID NO:
• 34 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 34, and a tenth condensation domain comprising the amino acid sequence as shown in SEQ ID NO:
• 35 or an amino acid sequence having 90% or higher identity to the amino acid sequence as shown in SEQ ID NO:
• 35.