Novel hybrid tetracenomycins through combinatorial biosynthesis using a glycosyltransferase encoded by the elm genes in cosmid 16F4 and which shows a broad sugar substrate specificity
Novel hybrid tetracenomycins through combinatorial biosynthesis using a glycosyltransferase encoded by the elm genes in cosmid 16F4 and which shows a broad sugar substrate specificity
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DOI：
10.1021/ja981687e
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发表时间：
1998-10-21
影响因子：
15
通讯作者：
Rohr, J
中科院分区：
文献类型：
--
作者：
Wohlert, SE;Blanco, G;Rohr, J
粘粒16 F4含有橄榄链霉菌Tu 2353的25 kb的埃洛霉素生物合成途径。将该粘粒转化到乌达霉素生产者的聚酮合酶（PKS）缺失突变体中，FragrantisTu 2717/Delta PKS和转化到光辉霉素生产者Streptomycesargillaceus ATCC 12956中，产生了几种新的糖基化四烯霉素。阐明了这些埃洛霉素类似物的四种结构（3，5-7）。它们携带不同的脱氧糖部分（D-橄榄糖、L-玫瑰糖、D-真菌糖和由两个1，3-连接的D-橄榄糖组成的二糖），连接在同一糖苷配基8-去甲基四环霉素C的C-8-O上（4）。fragrance或S.由于新的杂合四环霉素也由S.携带粘粒16 F4但缺乏所有已知的光神霉素糖基转移酶的黏菌突变体。此外，含有粘粒16 F4的变铅青链霉菌菌株仅在含有克隆的光辉霉素糖生物合成基因但缺乏糖基转移酶基因的第二质粒也存在时才产生新的四环素。因此，糖基转移必须由粘粒16 F4编码的埃洛霉素糖基转移酶催化。显然，这种糖基转移酶能够使用包括二糖在内的各种D-和L-糖催化8-去甲基四烯霉素C（4，= 12 a-去甲基内霉素酮）的糖基化。它的组合生物合成方法的未来用途进行了讨论。
Cosmid 16F4 contains 25 kb of the elloramycin biosynthetic pathway of Streptomyces olivaceus Tu2353. Transformation of this cosmid into a polyketide synthase (PKS)-deleted mutant of the urdamycin producer, Streptomyces fradiae Tu2717/Delta PKS and into the mithramycin producer Streptomyces argillaceus ATCC 12956 resulted in the production of several novel glycosylated tetracenomycins. Four of the structures of these elloramycin analogues (3, 5-7) were elucidated. They carry various deoxysugar moieties (D-olivose, L-rhodinose, D-mycarose, and a disaccharide consisting of two 1,3-linked D-olivoses) attached at C-8-O of the same aglycon, 8-demethyltetracenomycin C (4), The transfer of the sugars is not catalyzed by glycosyltransferases of the S. fradiae or S. argillaceus strains since the novel hybrid tetracenomycins are also produced by a S. argillaceus mutant carrying cosmid 16F4 but lacking all the known mithramycin glycosyltransferases. Furthermore, a Streptomyces lividans strain containing cosmid 16F4 produced the novel tetracenomycins only when a second plasmid containing the cloned mithramycin sugar biosynthetic genes bur lacking glycosyltransferase genes was also present. The glycosyl transfer therefore must be catalyzed by an elloramycin glycosyltransferase encoded by cosmid 16F4. Apparently, this glycosyltransferase is able to catalyze the glycosylation of 8-demethyltetracenomycin C (4, = 12a-demethylelloramycinone) using various D- and L-sugars including a disaccharide. Its future use for combinatorial biosynthetic approaches is discussed.