Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Nat Microbiol. 2019 Apr;4(4):587-594. doi: 10.1038/s41564-018-0345-x. Epub 2019 Jan 28.
The peptidoglycan cell wall is essential for the survival and morphogenesis of bacteria. For decades, it was thought that only class A penicillin-binding proteins (PBPs) and related enzymes effected peptidoglycan synthesis. Recently, it was shown that RodA-a member of the unrelated SEDS protein family-also acts as a peptidoglycan polymerase. Not all bacteria require RodA for growth; however, its homologue, FtsW, is a core member of the divisome complex that appears to be universally essential for septal cell wall assembly. FtsW was previously proposed to translocate the peptidoglycan precursor lipid II across the cytoplasmic membrane. Here, we report that purified FtsW polymerizes lipid II into peptidoglycan, but show that its polymerase activity requires complex formation with its partner class B PBP. We further demonstrate that the polymerase activity of FtsW is required for its function in vivo. Thus, our findings establish FtsW as a peptidoglycan polymerase that works with its cognate class B PBP to produce septal peptidoglycan during cell division.
肽聚糖细胞壁是细菌生存和形态发生所必需的。几十年来，人们一直认为只有 A 类青霉素结合蛋白（PBPs）和相关酶才能影响肽聚糖的合成。最近，研究表明，RodA-一种不相关的 SEDS 蛋白家族的成员-也作为肽聚糖聚合酶发挥作用。并非所有细菌的生长都需要 RodA；然而，它的同源物 FtsW 是分裂体复合物的核心成员，该复合物似乎普遍对隔膜细胞壁组装至关重要。FtsW 先前被提议将肽聚糖前体脂质 II 穿过细胞质膜转运。在这里，我们报告纯化的 FtsW 将脂质 II 聚合成长肽聚糖，但表明其聚合酶活性需要与其伴侣 B 类 PBP 形成复合物。我们进一步证明，FtsW 的聚合酶活性是其在体内功能所必需的。因此，我们的发现确立了 FtsW 作为一种肽聚糖聚合酶，它与同源的 B 类 PBP 一起在细胞分裂过程中产生隔膜肽聚糖。
