Kaneshiro Edna S
Department of Biological Sciences, University of Cincinnati, Ohio 45221, USA.
J Eukaryot Microbiol. 2002 Sep-Oct;49(5):367-73. doi: 10.1111/j.1550-7408.2002.tb00214.x.
Pneumocystis, an AIDS-associated opportunistic pathogen of the lung has some unusual features. This article focuses on work done by my group to understand the organism's distinct sterols. Although Pneumocystis is closely related to fungi, it lacks the major fungal sterol, ergosterol. Several delta(7) 24-alkysterols synthesized by P. carinii are the same as those reported in some basidiomycete rust fungi. The 24-alkylsterols are synthesized by the action of S-adenosyl-L-methionine:C-24 sterol methyl transferase (SAM:SMT). Fungal SAM:SMT enzymes normally transfer only one methyl group to the C-24 position of the sterol side chain and the cells accumulate C28 24-alkylsterols. In contrast, the P. carinii SAM:SMT and those of some plants catalyze one or two methyl transfer reactions producing both C28 and C29 24-alkylsterols. However, unlike most fungi, plants, and the kinetoplastid flagellates Leishmania and Trypanosoma cruzi, P. carinii does not appear to form double bonds at C-5 of the sterol nucleus and C-22 of the sterol side chain. Furthermore, the P. carinii SAM:SMT substrate preference for C30 lanosterol differs from that of homologous enzymes in any other organisms studied. C31 24-Methylenelanosterol and C32 pneumocysterol, products of SAM:SMT activity on lanosterol, can accumulate in high amounts in some, but not all, human-derived Pneumocystis jiroveci populations.
肺孢子菌是一种与艾滋病相关的肺部机会性致病原,具有一些不同寻常的特征。本文重点介绍了我的研究小组为了解该生物体独特的甾醇所做的工作。尽管肺孢子菌与真菌密切相关,但它缺乏主要的真菌甾醇——麦角甾醇。卡氏肺孢子菌合成的几种Δ(7) 24-烷基甾醇与一些担子菌锈菌中报道的相同。24-烷基甾醇是由S-腺苷-L-甲硫氨酸:C-24甾醇甲基转移酶(SAM:SMT)的作用合成的。真菌SAM:SMT酶通常只将一个甲基转移到甾醇侧链的C-24位置,细胞积累C28 24-烷基甾醇。相比之下,卡氏肺孢子菌的SAM:SMT和一些植物的SAM:SMT催化一个或两个甲基转移反应,产生C28和C29 24-烷基甾醇。然而,与大多数真菌、植物以及动基体鞭毛虫利什曼原虫和克氏锥虫不同,卡氏肺孢子菌似乎不在甾醇核的C-5和甾醇侧链的C-22处形成双键。此外,卡氏肺孢子菌的SAM:SMT对C30羊毛甾醇的底物偏好与其他任何研究过的生物体中的同源酶不同。SAM:SMT对羊毛甾醇的活性产物C31 24-亚甲基羊毛甾醇和C32肺孢子甾醇,在一些但不是所有源自人类的耶氏肺孢子菌群体中可以大量积累。