Spröte Petra, Brakhage Axel A
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Beutenbergstrasse 11a, 07745 Jena, Germany.
Arch Microbiol. 2007 Jul;188(1):69-79. doi: 10.1007/s00203-007-0224-y. Epub 2007 Mar 21.
The biosynthesis of the beta-lactam antibiotic penicillin in Aspergillus nidulans is catalysed by three enzymes that are encoded by the genes acvA, ipnA and aatA. Several studies have indicated that these genes are controlled by a complex regulatory network, including a variety of cis-acting DNA elements and regulatory factors. Until now, however, relatively little information is available on external signals and their transmission influencing the expression of the structural genes. Here, we show that the light-dependent regulator velvet A (VeA) acts as a repressor on the penicillin biosynthesis, mainly via repression of the acvA gene. Expression of a regulatable alcAp-veA gene fusion in an A. nidulans strain carrying, in addition, acvAp-uidA and ipnAp-lacZ gene fusions indicated that under alcAp-inducing conditions, penicillin titres and expression of acvAp-uidA were drastically reduced compared with untransformed wild-type strains. The same level of repression was found irrespective of whether the alcAp-veA gene fusion was expressed in a veA1 or DeltaveA background, with or without light. The expression of the ipnAp-lacZ gene fusion was only moderately affected indicating a less prominent effect. These findings were confirmed by the analysis of a regulatable niiAp-veA gene fusion. Under niiAp-inducing conditions, penicillin titres and acvAp-uidA expression were much lower than in untransformed wild-type strains.
构巢曲霉中β-内酰胺抗生素青霉素的生物合成由acvA、ipnA和aatA基因编码的三种酶催化。多项研究表明,这些基因受一个复杂的调控网络控制,该网络包括多种顺式作用DNA元件和调控因子。然而,到目前为止,关于影响结构基因表达的外部信号及其传递的信息相对较少。在此,我们表明光依赖调节因子天鹅绒A(VeA)作为青霉素生物合成的阻遏物,主要通过抑制acvA基因起作用。在携带acvAp-uidA和ipnAp-lacZ基因融合的构巢曲霉菌株中表达可调控的alcAp-veA基因融合表明,在alcAp诱导条件下,与未转化的野生型菌株相比,青霉素产量和acvAp-uidA的表达大幅降低。无论alcAp-veA基因融合是在veA1或ΔveA背景下表达,有无光照,都发现了相同程度的抑制作用。ipnAp-lacZ基因融合的表达仅受到中度影响,表明其作用不太显著。对可调控的niiAp-veA基因融合的分析证实了这些发现。在niiAp诱导条件下,青霉素产量和acvAp-uidA表达远低于未转化的野生型菌株。