Identification of the novel penicillin biosynthesis gene aatB of Aspergillus nidulans and its putative evolutionary relationship to this fungal secondary metabolism gene cluster

Identification of the novel penicillin biosynthesis gene aatB of Aspergillus nidulans and its putative evolutionary relationship to this fungal secondary metabolism gene cluster
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构巢曲霉新青霉素生物合成基因aatB的鉴定及其与该真菌次生代谢基因簇的推定进化关系

DOI:
10.1111/j.1365-2958.2008.06422.x
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发表时间:
2008
影响因子:
3.6
通讯作者:
A. Brakhage
A. Brakhage
中科院分区:
生物学2区
文献类型:
--
作者:
Petra Sproete;M. Hynes;P. Hortschansky;E. Shelest;Daniel H. Scharf;S. Wolke;A. Brakhage

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丝状真菌中性曲霉合成青霉素的最后一步是由aatA基因编码的异霉素N酰基转移酶催化。由于没有细菌同源物,它的进化起源仍然不清楚。如图所示,aatA的破坏仍然使青霉素的生产成为可能。基因组挖掘发现了与aatA具有相似结构和表达模式的aatB基因(AN6775.3)。aatB的破坏导致青霉素滴度降低。表面等离子体共振分析和Northern blot分析表明,aatA和aatB的启动子受相同的转录因子AnCF和anbhh1f的结合和调控。与aatA相反,aatB不编码过氧化物酶体靶向信号(PTS1)。在aatA破坏菌株中过度表达突变的aatBPTS1基因(导致AatB过氧化物酶体定位)比过度表达野生型AatB更能提高青霉素滴度。aatA的同源物仅是青霉素生物合成基因簇的一部分,而aatB的同源物也存在于非生产真菌中。我们的研究结果表明,aatB是aatA的一个平行序列。他们通过招募生物合成基因及其基因复制的顺式调控位点,扩展了青霉素生物合成基因簇的进化模型。
The final step of penicillin biosynthesis in the filamentous fungus Aspergillus nidulans is catalysed by isopenicillin N acyltransferase encoded by the aatA gene. Because there is no bacterial homologue, its evolutionary origin remained obscure. As shown here, disruption of aatA still enabled penicillin production. Genome mining led to the discovery of the aatB gene (AN6775.3) which has a similar structure and expression pattern as aatA. Disruption of aatB resulted in a reduced penicillin titre. Surface plasmon resonance analysis and Northern blot analysis indicated that the promoters of both aatA and aatB are bound and regulated by the same transcription factors AnCF and AnBH1f. In contrast to aatA, aatB does not encode a peroxisomal targeting signal (PTS1). Overexpression of a mutated aatBPTS1 gene in an aatA‐disruption strain (leading to peroxisomal localization of AatB) increased the penicillin titre more than overexpression of the wild‐type aatB. Homologues of aatA are exclusively part of the penicillin biosynthesis gene cluster, whereas aatB homologues also exist in non‐producing fungi. Our findings suggest that aatB is a paralogue of aatA. They extend the model of evolution of the penicillin biosynthesis gene cluster by recruitment of a biosynthesis gene and its cis‐regulatory sites upon gene duplication.
通过亚功能化保存重复基因的概率。
DOI: 10.1093/genetics/154.1.459
发表时间: 2000
期刊: Genetics
影响因子: 3.3
作者:
Lynch,M;Force,A
通讯作者: Force,A