The SARP Family Regulator Txn9 and Two-Component Response Regulator Txn11 are Key Activators for Trioxacarcin Biosynthesis in Streptomycesbottropensis
The SARP Family Regulator Txn9 and Two-Component Response Regulator Txn11 are Key Activators for Trioxacarcin Biosynthesis in Streptomycesbottropensis
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DOI：
10.1007/s00284-015-0868-9
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发表时间：
2015-07
影响因子：
2.6
通讯作者：
Kui Yang;Li-Hua Qi;Mei Zhang;Xian-Feng Hou;Hai-Xue Pan;G. Tang;Wei Wang;Hua Yuan
中科院分区：
文献类型：
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作者：
Kui Yang;Li-Hua Qi;Mei Zhang;Xian-Feng Hou;Hai-Xue Pan;G. Tang;Wei Wang;Hua Yuan
Trioxacarcin A是一种由链霉菌属产生的多氧、结构复杂的抗生素，其具有很高的抗菌、抗疟疾和抗肿瘤活性。trioxacarcin生物合成途径涉及具有1-异亮氨酸作为独特起始单元的II型聚酮酶（PKS），以及许多复杂的PKS后剪裁酶和抗性和调节蛋白。在这项工作中，两个调控基因，txn 9编码的链霉菌抗生素调控蛋白家族的调节器和txn 11的双组分反应调节器，被发现是绝对需要的三恶卡菌素生产通过单独失活所有六个注释的调控基因在txn集群。互补试验表明，这两种激活剂不存在调节级联关系。此外，转录分析表明，它们激活28个txnoperons中的15个，表明一个复杂的调控网络参与了trioxacarcin的生产。从这项研究中获得的信息可能有助于提高生产的高度有效的trioxacarcin A。
Trioxacarcin A is a polyoxygenated, structurally complex antibiotic produced byStreptomycesspp., which possesses high anti-bacterial, anti-malaria, and anti-tumor activities. The trioxacarcin biosynthetic pathway involves type II polyketide synthases (PKSs) withl-isoleucine as a unique starter unit, as well as many complex post-PKS tailoring enzymes and resistance and regulatory proteins. In this work, two regulatory genes,txn9coding for aStreptomycesantibiotic regulatory protein family regulator andtxn11for a two-component response regulator, were revealed to be absolutely required for trioxacarcin production by individually inactivating all the six annotated regulatory genes in thetxncluster. Complementation assay suggested that these two activators do not have a regulatory cascade relationship. Moreover, transcriptional analysis showed that they activate 15 of the 28txnoperons, indicating that a complicated regulatory network is involved in the trioxacarcin production. Information gained from this study may be useful for improving the production of the highly potent trioxacarcin A.