Maiya Shubha, Grundmann Alexander, Li Shu-Ming, Turner Geoffrey
University of Sheffield, Department of Molecular Biology and Biotechnology, Western Bank, UK.
Chembiochem. 2006 Jul;7(7):1062-9. doi: 10.1002/cbic.200600003.
A gene encoding a putative dimodular nonribosomal peptide synthetase (NRPS) was identified within a gene cluster of Aspergillus fumigatus, a species reported to produce fumitremorgins and other prenylated alkaloids. The gene was deleted and overexpressed in the genome reference strain Af293, and was also expressed in the naïve host Aspergillus nidulans, which lacks the equivalent gene cluster. While neither fumitremorgins nor the dipeptide brevianamide F (cyclo-L-Trp-L-Pro), an early intermediate, were detected in wild-type and deletion strains of A. fumigatus, brevianamide F accumulated in fungal cultures following increased expression of the NRPS gene in both A. fumigatus and A. nidulans. We conclude that the gene Afu8g00170, named ftmA, encodes the NRPS brevianamide synthetase. Brevianamide F is the precursor of a variety of fungal prenylated alkaloids with biological activity, including fumitremorgins A, B and C and tryprostatin B.
在烟曲霉的一个基因簇中鉴定出一个编码假定双模块非核糖体肽合成酶(NRPS)的基因,据报道该物种能产生烟曲霉震颤素及其他异戊烯化生物碱。该基因在基因组参考菌株Af293中被敲除和过表达,并且也在缺乏等效基因簇的原始宿主构巢曲霉中表达。虽然在烟曲霉的野生型和缺失菌株中均未检测到烟曲霉震颤素和早期中间体二肽短杆菌肽F(环-L-色氨酸-L-脯氨酸),但在烟曲霉和构巢曲霉中,随着NRPS基因表达增加,短杆菌肽F在真菌培养物中积累。我们得出结论,命名为ftmA的基因Afu8g00170编码NRPS短杆菌肽合成酶。短杆菌肽F是多种具有生物活性的真菌异戊烯化生物碱的前体,包括烟曲霉震颤素A、B和C以及曲古抑菌素B。