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通过甲羟戊酸非依赖途径的类异戊二烯生物合成,抗菌药物的新靶点?

Isoprenoid biosynthesis via the mevalonate-independent route, a novel target for antibacterial drugs?

作者信息

Rohmer M

机构信息

Université Louis Pasteur CNRS, Institut Le Bel, Strasbourg, France.

出版信息

Prog Drug Res. 1998;50:135-54. doi: 10.1007/978-3-0348-8833-2_3.

DOI:10.1007/978-3-0348-8833-2_3
PMID:9670778
Abstract

Mevalonate was accepted as the universal precursor of all isoprenoids. This assertion was however revealed to be partially incorrect. Incorporation of 13C labeled acetate and glucose into bacterial triterpenoids of the hopane series allowed for the discovery and the partial elucidation of a novel biosynthetic pathway leading to isopentenyl diphosphate. The C5 skeleton of isoprenic units results from the condensation of (hydroxyethyl)thiamin on the carbonyl group of glyceraldehyde 3-phosphate, yielding D-1-deoxyxylulose 1-phosphate. A subsequent intramolecular rearrangement is involved in the formation of the branched isoprenic skeleton. 2C-Methyl-D-erythritol (or its mono- or diphosphate) was shown to be a putative intermediate. This pathway is widespread in bacteria including opportunistic pathogens or innocuous species related to well-known pathogens. In plants, it is involved in the formation of essential chloroplast isoprenoids (carotenoids, phytol, plastoquinone) and of probably most other plastid related isoprenoids of more restricted distribution (isoprene, mono- and diterpenoids). Therefore it potentially represents a novel target for antibacterial drugs and herbicides.

摘要

甲羟戊酸曾被认为是所有类异戊二烯的通用前体。然而,这一论断后来被证明部分是错误的。将13C标记的乙酸盐和葡萄糖掺入细菌藿烷系列的三萜类化合物中,使得一条通往异戊烯基二磷酸的新生物合成途径得以发现并部分阐明。异戊二烯单元的C5骨架是由(羟乙基)硫胺素与3-磷酸甘油醛的羰基缩合而成,生成D-1-脱氧木酮糖1-磷酸。随后的分子内重排参与了支链异戊二烯骨架的形成。2C-甲基-D-赤藓糖醇(或其单磷酸酯或二磷酸酯)被证明是一种假定的中间体。这条途径在细菌中广泛存在,包括机会致病菌或与知名病原体相关的无害物种。在植物中,它参与必需叶绿体类异戊二烯(类胡萝卜素、叶绿醇、质体醌)以及可能大多数其他分布较窄的与质体相关的类异戊二烯(异戊二烯、单萜和二萜)的形成。因此,它可能代表了抗菌药物和除草剂的一个新靶点。

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