Action Mechanism of the Antibiotic Thiolactomycin

硫代actomycin选择性抑制细菌和植物的i型脂肪酸合成酶。利用细菌酶系统和植物酶系统，研究了硫霉素对脂肪酸合成酶系统的作用模式。在脂肪酸合成酶系统的6个单独酶中，[酰基-载体蛋白]（ACP）乙酰转移酶和3-氧酰基-ACP合成酶被硫霉素抑制。另一方面，其他酶不受这种抗生素的影响。硫霉素对脂肪酸合成酶系统的抑制是可逆的。对ACP乙酰转移酶的抑制对ACP呈竞争性，对乙酰辅酶a呈非竞争性。3-氧酰基- acp合成酶对丙二酰- acp具有竞争性抑制，对乙酰- acp .2无竞争性抑制。研究了硫代霉素对铜绿假单胞菌m507脂肪酸组成的影响。铜绿假单胞菌的主要脂肪酸为棕榈酸、棕榈油酸和异丙酸，次要脂肪酸为肉豆蔻酸和硬脂酸。随着硫霉素浓度的增加，棕榈油酸与异丙酸的比值增大。结果表明，棕榈油酸酯链延长疫苗接种对硫霉素比重新合成脂肪酸更敏感。硫代霉素抑制菠菜叶绿体和叶面草叶片脂肪酸合成。这种抗生素对棕榈酸向油酸的延伸比棕榈酸在菠菜叶绿体和草叶中的重新合成更有抑制作用。另一方面，TLM对豌豆种子硬脂酸进一步延伸为长链脂肪酸的抑制作用较小。抑制率依次为花生酸、白石蜡酸和木匠酸。

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.