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Gramicidin S or Gramicidin Soviet is an antibiotic effective against some Gram positive and Gram negative bacteria as well as some fungi. It is a derivative of gramicidin, produced by the Gram positive bacterium ''Bacillus brevis''. Gramicidin S is a cyclodecapeptide, constructed as two identical pentapeptides joined head to tail, formally written as ''cyclo''(-Val-Orn-Leu-D-Phe-Pro-)2. That is to say, it forms a ring structure composed of five different amino acids, each one used twice within the structure.〔 〕 Another interesting point is that it utilizes two amino acids uncommon in peptides: ornithine as well as the atypical stereoisomer of phenylalanine. It is synthesized by gramicidin S synthetase. == Biosynthesis == Gramicidin S biosynthetic pathway consists of two-enzyme of nonribosomal peptide synthases (NRPSs), gramicidin S synthetase I (GrsA) and gramicidin S synthetase II (GrsB), to give a product as a cyclic decapeptide. Within the biosynthetic pathway, there are total of five modules that specifically recognize, activate, and condense the amino acids to gramicidin S. Starting module GrsA consists of three domains: Adenylation (A) domain where it incorporates the amino acid and activates it by adenylation using ATP, Thiolation (T) domain or peptidyl carrier protein (PCP) in which the adenylated amino acid gets covalently attached to the 4´-phosphopantetheine group and this gets loaded onto the conserved serine in the T domain, Epimerization (E) domain where it epimerizes L-amino acid to D-amino acid. 〔Stachelhaus, T., & Marahiel, M. A. (1995). Modular structure of peptide synthetases revealed by dissection of the multifunctional enzyme GrsA. Journal of Biological Chemistry.〕 〔Döhren, von, H., Keller, U., Vater, J., & Zocher, R. (1997). Multifunctional Peptide Synthetases. Chemical Reviews, 97(7), 2675–2706.〕 〔Sieber, S. A., & Marahiel, M. A. (2005). Molecular mechanisms underlying nonribosomal peptide synthesis: approaches to new antibiotics. Chemical Reviews, 105(2), 715–738. http://doi.org/10.1021/cr0301191〕 Starting module GrsA loads D-Phe onto the system. Second enzyme cluster GrsB contains four modules, each containing condensation (C), adenylation (A), and thiolation (T) domains and thioesterase domain (TE) at the end. C domain forms a peptide bond between two amino acids, D-Phe and L-Pro. L-Val, L-Orn, and L-Leu are incorporated sequentially by the next three modules of GrsB. After repeating the whole module synthesis once again, TE domain cyclizes and releases the two peptides and dimerize them together to form the final product. 〔Miller, L. M., Mazur, M. T., McLoughlin, S. M., & Kelleher, N. L. (2005). Parallel interrogation of covalent intermediates in the biosynthesis of gramicidin S using high-resolution mass spectrometry. Protein Science : a Publication of the Protein Society, 14(10), 2702–2712. http://doi.org/10.1110/ps.051553705〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Gramicidin S」の詳細全文を読む スポンサード リンク
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