Hong Jay Sung Joong, Park Su Jin, Parajuli Niranjan, Park Sung Ryul, Koh Hwa Soo, Jung Won Seok, Choi Cha Yong, Yoon Yeo Joon
Interdisciplinary Program of Biochemical Engineering and Biotechnology, Seoul National University, San 56-1, Shilim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea.
Gene. 2007 Jan 15;386(1-2):123-30. doi: 10.1016/j.gene.2006.08.021. Epub 2006 Sep 12.
The DesVIII is an auxiliary protein which enhances the transfer of TDP-d-desosamine catalyzed by DesVII glycosyltransferase in the biosynthesis of macrolide antibiotics, neomethymycin, methymycin and pikromycin, in Streptomyces venezuelae ATCC 15439. Homologues of the desVIII gene are present in a number of aminosugar-containing antibiotic biosynthetic gene clusters including eryCII from the erythromycin producer Saccharopolyspora erythraea, oleP1 from the oleandomycin producer Streptomyces antibioticus, dnrQ from the doxorubicin producer Streptomyces peucetius, and tylMIII from the tylosin producer Streptomyces fradiae. In order to gain further insight into the function of these DesVIII homologues, interspecies complementation experiments were carried out by expressing each gene in a desVIII deletion mutant strain of S. venezuelae. Complementation by expressing EryCII, OleP1, and DnrQ in this mutant strain restored the production of glycosylated macrolides to an approximate level of 66%, 26% and 26%, respectively, compared to self-complementation by DesVIII. However, expression of TylMIII did not restore the antibiotic production. These results suggest that the DesVIII homologues (except for TylMIII) can functionally replace the native DesVIII for glycosylation to proceed in vivo and their functions are similar in acting as glycosyltransferase auxiliary proteins. The requirement of glycosyltransferase auxiliary protein seems to be more widespread in polyketide biosynthetic pathways than previously known.
DesVIII是一种辅助蛋白，在委内瑞拉链霉菌ATCC 15439中，它可增强DesVII糖基转移酶催化的TDP - d - 脱氧氨基糖转移反应，该反应参与大环内酯类抗生素新霉素、甲基霉素和苦霉素的生物合成。desVIII基因的同源物存在于许多含氨基糖的抗生素生物合成基因簇中，包括红霉素产生菌糖多孢红霉菌的eryCII、竹桃霉素产生菌抗生链霉菌的oleP1、阿霉素产生菌变铅青链霉菌的dnrQ以及泰乐菌素产生菌弗氏链霉菌的tylMIII。为了进一步深入了解这些DesVIII同源物的功能，通过在委内瑞拉链霉菌的desVIII缺失突变株中表达每个基因进行了种间互补实验。与DesVIII自身互补相比，在该突变株中表达EryCII、OleP1和DnrQ的互补作用分别将糖基化大环内酯的产量恢复到约66%、26%和26%的水平。然而，TylMIII的表达并未恢复抗生素的产量。这些结果表明，DesVIII同源物（除TylMIII外）在体内能够功能性替代天然DesVIII进行糖基化反应，并且它们作为糖基转移酶辅助蛋白的功能相似。糖基转移酶辅助蛋白的需求在聚酮生物合成途径中似乎比以前所知的更为普遍。
