Department of Chemistry, Boston University, Boston, MA 02215.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
Proc Natl Acad Sci U S A. 2021 Jan 26;118(4). doi: 10.1073/pnas.2018289118.
The monotopic phosphoglycosyl transferase (monoPGT) superfamily comprises over 38,000 nonredundant sequences represented in bacterial and archaeal domains of life. Members of the superfamily catalyze the first membrane-committed step in en bloc oligosaccharide biosynthetic pathways, transferring a phosphosugar from a soluble nucleoside diphosphosugar to a membrane-resident polyprenol phosphate. The singularity of the monoPGT fold and its employment in the pivotal first membrane-committed step allows confident assignment of both protein and corresponding pathway. The diversity of the family is revealed by the generation and analysis of a sequence similarity network for the superfamily, with fusion of monoPGTs with other pathway members being the most frequent and extensive elaboration. Three common fusions were identified: sugar-modifying enzymes, glycosyl transferases, and regulatory domains. Additionally, unexpected fusions of the monoPGT with members of the polytopic PGT superfamily were discovered, implying a possible evolutionary link through the shared polyprenol phosphate substrate. Notably, a phylogenetic reconstruction of the monoPGT superfamily shows a radial burst of functionalization, with a minority of members comprising only the minimal PGT catalytic domain. The commonality and identity of the fusion partners in the monoPGT superfamily is consistent with advantageous colocalization of pathway members at membrane interfaces.
单萜磷酸糖基转移酶（monoPGT）超家族包含超过 38000 个非冗余序列，分布于细菌和古菌领域的生命中。该超家族的成员催化整体寡糖生物合成途径中的第一个膜结合步骤，将磷酸糖从可溶性核苷二磷酸糖转移到膜驻留的多萜醇磷酸上。monoPGT 折叠的独特性及其在关键的第一个膜结合步骤中的应用，使得蛋白质和相应途径的归属具有高度可信度。通过对该超家族的序列相似性网络进行生成和分析，揭示了该家族的多样性，其中最常见和广泛的是 monoPGTs 与其他途径成员的融合。鉴定出三种常见的融合：糖修饰酶、糖基转移酶和调节结构域。此外，还发现了 monoPGT 与多萜基 PGT 超家族成员的意外融合，这暗示了通过共享多萜醇磷酸底物可能存在进化联系。值得注意的是，monoPGT 超家族的系统发育重建显示出功能化的径向爆发，少数成员仅包含最小的 PGT 催化结构域。monoPGT 超家族中融合伙伴的共性和同一性与途径成员在膜界面处的有利共定位一致。
