Characterization of a methyltransferase involved in herboxidiene biosynthesis

Characterization of a methyltransferase involved in herboxidiene biosynthesis
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参与草二烯生物合成的甲基转移酶的表征

DOI:
10.1016/j.bmcl.2013.08.023
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发表时间:
2013-10-15
影响因子:
2.7
通讯作者:
Zhan, Jixun
Zhan, Jixun
中科院分区:
医学4区
文献类型:
--
作者:
Yu, Dayu;Xu, Fuchao;Zhan, Jixun

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草氧化二烯生物合成基因簇包含一个调控基因和六个生物合成基因,其编码三种聚酮酶(HerB、HerC和HerD)和三种剪裁酶(HerE、HerF和HerG)。通过单交换重组,将整合型质粒插入到色褐链霉菌ATCC 49982基因组herE和herF之间,使herF和下游herG得到低水平表达。该突变株产生两个新化合物,18-脱氧-25-去甲基-草氧化二烯和25-去甲基-草氧化二烯。HerF在大肠杆菌中表达,其生物化学特征为在herboxidiene生物合成中的专用甲基转移酶。它偏好25-去甲基-herboxidiene比18-脱氧-25-去甲基-herboxidiene,表明C-25甲基化是最后的剪裁步骤。(C)2013爱思唯尔有限公司保留所有权利。
The herboxidiene biosynthetic gene cluster contains a regulatory gene and six biosynthetic genes that encode three polyketide synthases (HerB, HerC and HerD) and three tailoring enzymes (HerE, HerF and HerG). Through single crossover recombination, an integrative plasmid was inserted into the genome of Streptomyces chromofuscus ATCC 49982 between herE and herF, resulting in low-level expression of herF and the downstream herG. The mutant strain produced two new compounds, 18-deoxy-25-demethyl-herboxidiene and 25-demethyl-herboxidiene. HerF was expressed in Escherichia coli and biochemically characterized as the dedicated methyltransferase in herboxidiene biosynthesis. It prefers 25-demethyl-herboxidiene to 18-deoxy-25-demethyl-herboxidiene, suggesting that C-25 methylation is the last tailoring step. (C) 2013 Elsevier Ltd. All rights reserved.