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Action Mechanism of the Antibiotic Thiolactomycin

抗生素硫乳霉素的作用机制

基本信息

批准号：
60580127
负责人：
KAWAGUCHI Akihiko
金额：
$ 0.19万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60580127/
关键词：
Antibiotic Thiolactomycin 脂肪酸合成酵素

项目摘要

Thiolactomycin selectively inhibits type ll fatty acid svnthases of bacteria and plants. The mode of the thiolactomycin action on the fatty acid synthase systems was investigated using the enzyme systems of bacteria and plants.1. Of the six individual enzymes of the fatty acid synthase system, [acyl-carrier-protein] (ACP) acetyltransferase and 3-oxoacyl-ACP synthase were inhibited by thiolactomycin. On the other hand,the other enzymes were not affected by this antibiotic. The thiolactomycin inhibition of the fatty acid synthase system was reversible. As to ACP acetyltransferase, the inhibition was competitive with respect to ACP and uncompetitive with respect to acetyl-CoA. As to 3-oxoacyl-ACP synthase, the inhibition was competitive with respect to malonyl-ACP and noncompetitive with respect to acetyl-ACP.2. The effects of thiolactomycin on fatty acid composition of Pseudomonas aeruginosa M 507 were studied. P.aeruginosa contained palmitic, palmitoleic and vaccenic acids as major fatty acids and myristic and stearic acids as minor fatty acids. The ratio of palmitoleic acid to vaccenic acid increased with increasing concentration of thiolactomycin. The results suggested that the chain elongation of palmitoleate to vaccenate is more sensitive to thiolactomycin than the de novo synthesis of fatty acids.3. Thiolactomycin inhibited fatty acid synthesis in both spinach chloroplasts and Avena leaves. This antibiotic is more inhibitory to the elongation of palmitic to oleic acid than de novo synthesis of palmitic acid in both spinach chloroplasts and Avena leaves. On the other hand, TLM is less inhibitory to further elongation of stearic acid to very long chain fatty acids in pea seeds. The inhibition rate decreased in the order of arachidic, behenic and lignoceric acid synthesized.

硫乳霉素选择性抑制细菌和植物的Ⅱ型脂肪酸合成酶。利用细菌和植物的脂肪酸合成酶系统研究硫乳霉素对脂肪酸合成酶系统的作用方式.在脂肪酸合成酶系统的六种酶中，[酰基载体蛋白]（ACP）乙酰转移酶和3-氧代酰基-ACP合成酶被硫代乳霉素抑制。另一方面，其他酶不受这种抗生素的影响。硫乳霉素对脂肪酸合成酶系统的抑制是可逆的。对ACP乙酰转移酶的抑制作用与ACP呈竞争性，与乙酰辅酶A呈非竞争性。对于3-氧代酰基-ACP合酶，丙二酰-ACP的抑制作用为竞争性，乙酰-ACP的抑制作用为非竞争性。研究了硫乳霉素对铜绿假单胞菌M507脂肪酸组成的影响.铜绿假单胞菌含有棕榈酸、棕榈油酸和异油酸作为主要脂肪酸，肉豆蔻酸和硬脂酸作为次要脂肪酸。棕榈油酸与异油酸的比例随硫乳霉素浓度的增加而增加。结果表明，棕榈油酸酯链的延长比脂肪酸的从头合成对硫乳霉素更敏感.硫乳霉素抑制菠菜叶绿体和燕麦叶片中脂肪酸的合成。这种抗生素对菠菜叶绿体和燕麦叶片中棕榈酸向油酸的延伸的抑制作用比棕榈酸的从头合成更强。另一方面，TLM对豌豆种子中硬脂酸进一步延伸为极长链脂肪酸的抑制性较小。花生酸、二十二烷酸和二十四烷酸对细胞生长的抑制率依次降低。