Sauerwald Anselm, Zhu Wenhong, Major Tiffany A, Roy Hervé, Palioura Sotiria, Jahn Dieter, Whitman William B, Yates John R, Ibba Michael, Söll Dieter
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
Science. 2005 Mar 25;307(5717):1969-72. doi: 10.1126/science.1108329.
Several methanogenic archaea lack cysteinyl-transfer RNA (tRNA) synthetase (CysRS), the essential enzyme that provides Cys-tRNA(Cys) for translation in most organisms. Partial purification of the corresponding activity from Methanocaldococcus jannaschii indicated that tRNA(Cys) becomes acylated with O-phosphoserine (Sep) but not with cysteine. Further analyses identified a class II-type O-phosphoseryl-tRNA synthetase (SepRS) and Sep-tRNA:Cys-tRNA synthase (SepCysS). SepRS specifically forms Sep-tRNA(Cys), which is then converted to Cys-tRNA(Cys) by SepCysS. Comparative genomic analyses suggest that this pathway, encoded in all organisms lacking CysRS, can also act as the sole route for cysteine biosynthesis. This was proven for Methanococcus maripaludis, where deletion of the SepRS-encoding gene resulted in cysteine auxotrophy. As the conversions of Sep-tRNA to Cys-tRNA or to selenocysteinyl-tRNA are chemically analogous, the catalytic activity of SepCysS provides a means by which both cysteine and selenocysteine may have originally been added to the genetic code.
几种产甲烷古菌缺乏半胱氨酰转移RNA(tRNA)合成酶(CysRS),而在大多数生物体中,这种关键酶能为翻译过程提供半胱氨酰tRNA(Cys-tRNA)。从詹氏甲烷球菌中部分纯化出相应活性表明,tRNA(Cys)是被O-磷酸丝氨酸(Sep)而非半胱氨酸酰化。进一步分析鉴定出一种II类O-磷酸丝氨酰-tRNA合成酶(SepRS)和丝氨酰-tRNA:半胱氨酰-tRNA合成酶(SepCysS)。SepRS特异性地形成丝氨酰-tRNA(Cys),然后由SepCysS将其转化为半胱氨酰-tRNA(Cys)。比较基因组分析表明,在所有缺乏CysRS的生物体中编码的这条途径,也可作为半胱氨酸生物合成的唯一途径。这在沼泽甲烷球菌中得到了证实,在那里,编码SepRS的基因缺失导致半胱氨酸营养缺陷。由于丝氨酰-tRNA向半胱氨酰-tRNA或硒代半胱氨酰-tRNA的转化在化学上是类似的,SepCysS的催化活性提供了一种方式,通过这种方式,半胱氨酸和硒代半胱氨酸最初都可能被添加到遗传密码中。