CYSTEINE BIOSYNTHESIS IN SACCHAROMYCES-CEREVISIAE OCCURS THROUGH THE TRANSSULFURATION PATHWAY WHICH HAS BEEN BUILT-UP BY ENZYME RECRUITMENT
CYSTEINE BIOSYNTHESIS IN SACCHAROMYCES-CEREVISIAE OCCURS THROUGH THE TRANSSULFURATION PATHWAY WHICH HAS BEEN BUILT-UP BY ENZYME RECRUITMENT
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DOI：
10.1128/jb.175.17.5366-5374.1993
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发表时间：
1993-09-01
影响因子：
3.2
通讯作者：
SURDINKERJAN, Y
中科院分区：
文献类型：
--
作者：
CHEREST, H;THOMAS, D;SURDINKERJAN, Y
硫化途径允许同型半胱氨酸和半胱氨酸相互转化，中间形成胱硫氨酸。到目前为止，所研究的各种生物将还原的硫合并到一个三碳或四碳的链中，并以不同的方式使用硫磺转化途径来合成含硫氨基酸。在肠道细菌中，半胱氨酸的合成是有机硫代谢的第一步，同型半胱氨酸是半胱氨酸的产物。真菌能够将还原的硫结合到一个四碳链中，并且它们有两条操作的硫磺转化途径。相比之下，从同型半胱氨酸合成半胱氨酸是哺乳动物现存的唯一的硫化途径。在酿酒酵母中，对突变体的遗传、表型和酶学研究使我们能够证明同型半胱氨酸是第一个合成的含硫氨基酸，半胱氨酸只能由同型半胱氨酸衍生(H.Cherest和Y.Surdin-Kerjan，Genetics 130：51-58,1992)。我们在此报道了分别编码胱硫醚β-合成酶和胱硫醚伽马裂解酶的基因STR4和STR1的克隆。STR1或STR4失活的唯一表型结果是半胱氨酸营养不良。STR4基因的测序使我们能够比较所有已知的转硫酶和催化碳链中还原硫掺入的酶的序列。这些比较揭示了基于序列基序的两个家族的划分。这种分配主要与这些酶的催化机制的相似性有关。
The transsulfuration pathways allow the interconversion of homocysteine and cysteine with the intermediary formation of cystathionine. The various organisms studied up to now incorporate reduced sulfur into a three- or a four-carbon chain and use differently the transsulfuration pathways to synthesize sulfur amino acids. In enteric bacteria, the synthesis of cysteine is the first step of organic sulfur metabolism and homocysteine is derived from cysteine. Fungi are capable of incorporating reduced sulfur into a four-carbon chain, and they possess two operating transsulfuration pathways. By contrast, synthesis of cysteine from homocysteine is the only existing transsulfuration pathway in mammals. In Saccharomyces cerevisiae, genetic, phenotypic, and enzymatic study of mutants has allowed us to demonstrate that homocysteine is the first sulfur amino acid to be synthesized and cysteine is derived only from homocysteine (H. Cherest and Y. Surdin-Kerjan, Genetics 130:51-58, 1992). We report here the cloning of genes STR4 and STR1, encoding cystathionine beta-synthase and cystathionine gamma-lyase, respectively. The only phenotypic consequence of the inactivation of STR1 or STR4 is cysteine auxotrophy. The sequencing of gene STR4 has allowed us to compare all of the known sequences of transsulfuration enzymes and enzymes catalyzing the incorporation of reduced sulfur in carbon chains. These comparisons reveal a partition into two families based on sequence motifs. This partition mainly correlates with similarities in the catalytic mechanisms of these enzymes.