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变铅青链霉菌中的dnrM基因含有一个自然发生的移码突变,该突变被柔红霉素生产基因簇外的另一个基因座所抑制。

The dnrM gene in Streptomyces peucetius contains a naturally occurring frameshift mutation that is suppressed by another locus outside of the daunorubicin-production gene cluster.

作者信息

Gallo Mark A, Ward Joanne, Hutchinson C R

机构信息

School of Pharmacy, University of Wisconsin, Madison, Wl 53706, USA.

Department of Bacteriology, University of Wisconsin, Madison, Wl 53706, USA.

出版信息

Microbiology (Reading). 1996 Feb;142 ( Pt 2):269-275. doi: 10.1099/13500872-142-2-269.

Abstract

A 2 center dot 7 kb BamHI fragment of the daunorubicin biosynthetic cluster in Streptomyces peucetius ATCC 29050 was shown to contain two ORFs, dnrL and dnrM, whose deduced products exhibit a high sequence similarity to a number of glucose-1-phosphate thymidylyl transferases and TDP-D-glucose dehydratases, respectively. Although these genes were believed to be necessary for the synthesis of the deoxyaminosugar, daunosamine, a constituent of daunorubicin, the dnrM gene contains a frameshift in the DNA sequence that causes the premature termination of translation. A gene encoding another TDP-glucose 4,6-dehydratase, previously isolated from S. peucetius, was identified by PCR amplification of genomic DNA. The presence of this gene explains why a dnrM::aphll mutation did not block daunorubicin production.

摘要

在变铅青链霉菌ATCC 29050中,柔红霉素生物合成簇的一个2.7 kb BamHI片段被证明含有两个开放阅读框dnrL和dnrM,其推导产物分别与多种葡萄糖-1-磷酸胸苷酰基转移酶和TDP-D-葡萄糖脱水酶表现出高度的序列相似性。尽管这些基因被认为是柔红霉素的组成成分脱氧氨基糖柔红糖胺合成所必需的,但dnrM基因在DNA序列中存在一个移码突变,导致翻译提前终止。通过基因组DNA的PCR扩增,鉴定出了另一个编码TDP-葡萄糖4,6-脱水酶的基因,该基因先前从变铅青链霉菌中分离得到。这个基因的存在解释了为什么dnrM::aphll突变不会阻断柔红霉素的产生。

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