枯草桿菌 F29-3 豐原素合成? FenC 與 Malony1-CoA 鍵結區域之探討

Studies on the malonyl-CoA binding site of fengycin synthetase FenC

蔡宗澔(TzungHao Tsai)

指導教授 ： 康世旭教授

元智大學/工程學院/生物科技暨生物資訊研究所/碩士(2005年)

摘要

無資料

關鍵字

豐原素 ； 脂肪酸支鏈

並列摘要

Abstract
Fengycin, an antifungal antibiotic produced by Bacillus subtilis F29-3, is a cyclic lipopeptidic antibiotic. This compound is produced by a series of enzymes, i.e., FenC, FenD, FenE, FenA, and FenB, underlying a nonribosomal mechanism of peptide synthesis. The structure of fengycin includes a cyclic polypeptide, consisted of one each of D-ornithine, L-tyrosine, D-allo-theronine, L-proline, D-tyrosine, L-isoleucine, D-alanine or D-valine, and three L-glutamic acids, and a fatty acid moiety linking to the N terminal of the peptide backbone. Although fengycin synthesis has been studied for about forty years, lots of details are not yet elucidated, including mechanisms underlying the initialization, elongation, and termination of peptide chain as well as the covalent conjugation of fatty acid moiety to the peptide backbone. Previous studies have showed that a malonyl-group, the precursor of fatty acid synthesis, could bind to the fengycin synthetase C (FenC), indicating that this phenomenon might be associated with the formation of fatty acid moiety in the nonribosomal peptide synthesis. In this thesis, three models were proposed to explain how the fatty acid moiety of fengycin might be synthesized. In order to determine which model is correct, the domain of FenC responsible for malonyl-CoA binding was clarified. The result showed that malonyl-CoA bound to the first thiolation domain of FenC, supporting the assumption of Model 3, that malonyl-CoA binds to the thiolation domain of each peptide synthetase. Both fatty acid and peptide chain are elongated simultaneously but independently until liking to the terminal enzyme, which catalyzes the linkage of peptide chain and fatty acid, and completes fengycin synthesis by releasing the product, an entire molecule of lipopeptidic antibiotic.

並列關鍵字

fengycin ； nonribosomal