Combinatorial biosynthesis of antitumor deoxysugar pathways in Streptomyces griseus:: Reconstitution of "unnatural natural gene clusters" for the biosynthesis of four 2,6-D-dideoxyhexoses

Combinatorial biosynthesis of antitumor deoxysugar pathways in Streptomyces griseus:: Reconstitution of "unnatural natural gene clusters" for the biosynthesis of four 2,6-D-dideoxyhexoses
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DOI:
10.1128/aem.01266-06
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发表时间:
2006-10-01
影响因子:
4.4
通讯作者:
Mendez, Carmen
Mendez, Carmen
中科院分区:
生物学2区
文献类型:
--
作者:
Perez, Maria;Lombo, Felipe;Mendez, Carmen

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将组合生物合成应用于链霉菌脱氧糖生物合成基因,以重构用于四种D-脱氧糖(D-橄榄糖、D-橄榄糖、D-洋地黄糖和D-博伊维糖)生物合成的“非天然天然基因簇”。这些基因簇在白色链霉菌16 F4中的表达用于通过产生糖基化的四烯霉素来证明所设计的簇的功能性。合成了3个糖基化的四环霉素,其中2个(D-洋地黄糖基-四环霉素C和D-葡萄糖基-四环霉素C)为新化合物。构建的基因簇可用于增加微生物合成新的脱氧糖的能力,从而产生新的糖基化生物活性化合物。
Combinatorial biosynthesis was applied to Streptomyces deoxysugar biosynthesis genes in order to reconstitute "unnatural natural gene clusters" for the biosynthesis of four D-deoxysugars (D-olivose, D-oliose, D-digitoxose, and D-boivinose). Expression of these gene clusters in Streptomyces albus 16F4 was used to prove the functionality of the designed clusters through the generation of glycosylated tetracenomycins. Three glycosylated tetracenomycins were generated and characterized, two of which (D-digitoxosyl-tetracenomycin C and D-boivinosyl-tetracenocmycin C) were novel compounds. The constructed gene clusters may be used to increase the capabilities of microorganisms to synthesize new deoxysugars and therefore to produce new glycosylated bioactive compounds.