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类异戊二烯生物合成作为抗菌和抗寄生虫药物的新靶点。

Isoprenoid biosynthesis as a novel target for antibacterial and antiparasitic drugs.

作者信息

Rohmer Michel, Grosdemange-Billiard Catherine, Seemann Myriam, Tritsch Denis

机构信息

Université Louis Pasteur CNRS, Institut Universitaire de France, Institut Le Bel, 4 rue Blaise Pascal 67070 Strasbourg Cedex, France.

出版信息

Curr Opin Investig Drugs. 2004 Feb;5(2):154-62.

Abstract

The mevalonate-independent methylerythritol phosphate pathway is a long overlooked metabolic pathway for isoprenoid biosynthesis. It is present in most bacteria, including pathogens and opportunistic pathogens, in some unicellular eukaryotes, including the parasite responsible for malaria, and in the chloroplasts of all phototrophic organisms. It represents an alternative to the mevalonate pathway, which is only present in animals, fungi, the plant cytoplasm, archaebacteria and some eubacteria. This biosynthetic pathway is thus a potential target for antibacterial and antiparasitic drugs. An isopentenyl diphosphate isomerase that differs from the previously known isopentenyl diphosphate isomerase found in all other organisms, including animals, was discovered in several Gram-positive bacteria possessing the mevalonate pathway, adding another target related to isoprenoid biosynthesis.

摘要

不依赖甲羟戊酸的甲基赤藓糖醇磷酸途径是一条长期被忽视的类异戊二烯生物合成代谢途径。它存在于大多数细菌中,包括病原体和机会致病菌,在一些单细胞真核生物中也有,比如引发疟疾的寄生虫,并且存在于所有光合生物的叶绿体中。它是甲羟戊酸途径的一种替代途径,甲羟戊酸途径仅存在于动物、真菌、植物细胞质、古细菌和一些真细菌中。因此,这条生物合成途径是抗菌和抗寄生虫药物的潜在靶点。在几种具有甲羟戊酸途径的革兰氏阳性细菌中发现了一种异戊烯基二磷酸异构酶,它与在包括动物在内的所有其他生物中发现的先前已知的异戊烯基二磷酸异构酶不同,这又增加了一个与类异戊二烯生物合成相关的靶点。

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