REGULATION OF HEME-BIOSYNTHESIS IN ESCHERICHIA-COLI
REGULATION OF HEME-BIOSYNTHESIS IN ESCHERICHIA-COLI
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DOI：
10.1006/abbi.1995.1016
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发表时间：
1995-01-10
影响因子：
3.9
通讯作者：
DAILEY, HA
中科院分区：
文献类型：
--
作者：
WOODARD, SI;DAILEY, HA
大肠杆菌是一种从谷氨酸（C-5途径）合成5-氨基酮戊酸（ALA）的生物，5-氨基酮戊酸是血红素生物合成途径的第一个关键化合物，而不是从甘氨酸和琥珀酰CoA（C-4途径）合成。虽然人们普遍认为C-4途径的调节发生在ALA的形成水平，但C-5途径的调节模式目前尚不清楚。在这里，我们研究了血红素合成的调控在E。大肠杆菌：作用的最终产品，血红素，作为一个反馈调节ALA生产。通过使用在野生型E.大肠杆菌菌株中，有可能确定所提出的调节血红素库在ALA和血红素产生的调节中所起的作用。大鼠可溶性细胞色素bg的表达导致细胞血红素的增加，表明细胞通过产生更多的血红素来响应这种外来的“血红素库”，即使细胞色素不直接参与正常的细胞调节。在这些条件下不会发生途径中间体的积累。质粒编码的小鼠ALA合酶的表达导致细胞血红素产生增加以及在存在或不存在质粒编码的细胞色素B的情况下途径中间体的积累（5）。这些数据支持一种调节方案，其中该C-5生物体中的血红素生物合成途径在ALA产生的水平上部分地通过细胞血红素含量来调节，（C）1995 Academic Press，Inc.
Escherichia coli is an organism that synthesizes 5-aminolevulinate (ALA), the first committed compound of the heme biosynthetic pathway, from glutamate (C-5 pathway) as opposed to glycine and succinyl CoA (C-4 pathway), While regulation of the C-4 pathway is generally acknowledged to occur at the level of formation of ALA, the mode of regulation of the C-5 pathway is currently unclear. Here we have examined one aspect of regulation of heme synthesis in E. coli: the role of the end product, heme, as a feed-back regulator of ALA production. By using plasmid-encoded ALA synthase and/or cytochrome b(5) expressed in a wild type E. coli strain, it was possible to determine the role that the proposed regulatory heme pool plays in the regulation of ALA and heme production, Expression of rat-soluble cytochrome bg results in an increase of cellular heme, indicating that the cell responds to this foreign ''heme sink'' by producing more heme even though the cytochrome does not participate directly in normal cellular regulation. Accumulation of pathway intermediates does not occur under these conditions, Expression of plasmid-encoded mouse ALA synthase results in increased cellular heme production as well as the accumulation of pathway intermediates either in the presence or absence of plasmid encoded cytochrome b(5). These data support a regulatory scheme where the heme biosynthetic pathway in this C-5 organism is regulated at the level of ALA production in part by cellular heme content, (C) 1995 Academic Press, Inc.