Cloning and Sequencing of the Biosynthetic Gene Cluster for Saquayamycin Z and Galtamycin B and the Elucidation of the Assembly of Their Saccharide Chains
Cloning and Sequencing of the Biosynthetic Gene Cluster for Saquayamycin Z and Galtamycin B and the Elucidation of the Assembly of Their Saccharide Chains
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DOI：
10.1002/cbic.200900054
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发表时间：
2009-05-25
期刊：
影响因子：
3.2
通讯作者：
Bechthold, Andreas
中科院分区：
文献类型：
--
作者：
Erb, Annette;Luzhetskyy, Andriy;Bechthold, Andreas
革兰氏阳性细菌，小单孢菌属。 Tu6368 产生安古环抗生素 saquayamycin Z 和并四苯醌加他霉素 B。这两种化合物的结构相似性表明了共同的生物合成途径。克隆并表征了整个生物合成基因簇（saq 基因簇）。对 36.7 kb 区域的 DNA 序列分析揭示了 31 个基因的存在，这些基因可能与 saquayamycin Z 和加他霉素 B 的形成有关。进行异源表达实验和靶向基因失活，以特异性操纵saquayamycin Z和galtamycin B途径；这明确证明这两种化合物源自同一簇。糖基转移酶基因的失活导致新型沙夸霉素和加他霉素衍生物的产生，提供了糖链组装的信息，并表明并四苯醌是由安古环素形成的。
The Gram-positive bacterium, Micromonospora sp. Tu6368 produces the angucyclic antibiotic saquayamycin Z and the tetracenequinone galtamycin B. The structural similarity of both compounds suggests a common biosynthetic pathway. The entire biosynthetic gene cluster (saq gene cluster) was cloned and characterized. DNA sequence analysis of a 36.7 kb region revealed the presence of 31 genes that are probably involved in saquayamycin Z and galtamycin B formation. Heterologous expression experiments and targeted gene inactivations were carried out to specifically manipulate the saquayamycin Z and galtamycin B pathways; this demonstrated unambiguously that both compounds are derived from the same cluster. The inactivation of glycosyltransferase genes led to the production of novel saquayamycin and galtamycin derivatives, provided information on the assembly of the sugar chains, and showed that tetracenequinones are formed from angucyclines.