Functional characterization of the early steps of tetrapyrrole biosynthesis and modification in Desulfovibrio vulgaris Hildenborough
Functional characterization of the early steps of tetrapyrrole biosynthesis and modification in Desulfovibrio vulgaris Hildenborough
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DOI：
10.1042/bj20090151
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发表时间：
2009-06-01
影响因子：
4.1
通讯作者：
Saraiva, Ligia M.
中科院分区：
文献类型：
--
作者：
Lobo, Susana A. L.;Brindley, Amanda;Saraiva, Ligia M.
四吡咯框架的生物合成已在硫酸盐还原菌脱硫弧菌Hildenborough的氨基乙酰丙酸转化为sirohydrochlorin所需的酶的特性进行了研究。PBG（胆色素原）合酶（HemB）被发现是锌依赖性酶，以其天然状态存在，作为一个homohexamer。PBG脱氨酶（HemC）被证明含有二吡咯甲烷辅因子。发现尿卟啉原III合酶与尿卟啉原III甲基转移酶（HemD-CobA）融合。这两种活性都可以在这种合并的蛋白质中得到证明，并且通过解剖相关基因来分离各个酶活性，以允许产生两种不同的蛋白质。在基因组中注释为双功能前咕啉-2脱氢酶/西罗氢二氢卟啉铁螯合酶的基因在I act中显示仅作为脱氢酶起作用，并且仅能够合成西罗氢二氢卟啉而不是西罗血红素。基因组分析还揭示了缺乏任何尿卟啉原III脱羧酶，所有的酶都是合成血红素的经典途径所必需的。然而，尽管细菌不含cd（1）硝酸还原酶，但其基因组确实编码了预测的血红素d（1）生物合成酶。我们认为西罗氢二氢卟啉作为血红素合成的底物，使用了一种涉及d（1）生物合成系统同源物的新途径。这解释了为什么发现尿卟啉原III合酶与甲基转移酶融合，而不需要尿卟啉原III脱羧酶活性。
The biosynthesis of the tetrapyrrole framework has been investigated in the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough by characterization of the enzymes required for the transformation of aminolaevulinic acid into sirohydrochlorin. PBG (porphobilinogen) synthase (HemB) was found to be at zinc-dependent enzyme that exists in its native state as a homohexamer. PBG deaminase (HemC) was shown to contain the dipyrromethane cofactor. Uroporphyrinogen III synthase is found fused with a uroporphyrinogen III methyltransferase (HemD-CobA). Both activities Could be demonstrated in this amalgamated protein and the individual enzyme activities were separated by dissecting the relevant gene to allow the production of two distinct proteins. A gene annotated in the genome as a bifunctional precorrin-2 dehydrogenase/sirohydrochlorin ferrochelatase was in I act shown to act only as a dehydrogenase and is simply capable of synthesizing sirohydrochlorin rather than sirohaem. Genome analysis also reveals a lack of any uroporphyrinogen Ill decarboxylase, all enzyme necessary for the classical route to heam synthesis. However, tile genome does encode soiree predicted haem d(1) biosynthetic enzymes even though tile bacterium does not contain the cd(1) nitriate reductase, We suggest that sirohydrochlorin acts as a substrate for heam synthesis using a novel pathway that involves homologues of the d(1) biogenesis system. This explains why the uroporphyrinogen III synthase is found fused with tile methyltransferase, bypassing tile need for uroporphyrinogen III decarboxylase activity.