Improved tryprostatin B production by heterologous gene expression in Aspergillus nidulans.
Tryprostatin B, a prenylated diketopiperazine with anti-tubulin activity, has been overproduced in fungal culture by expression of genes of the fumitremorgin cluster from Aspergillus fumigatus in the naïve host Aspergillus nidulans using the alcA promoter. The products of the expressed genes catalyse the first two steps of fumitremorgin biosynthesis, namely the formation of brevianamide F and its conversion to tryprostatin B. Yields of tryprostatin B were up to 250 mg/l, a significant improvement in previously reported levels. This approach illustrates how the availability of fungal genome sequences and knowledge of gene function can be used to achieve the efficient production of biologically active secondary metabolites by genetic manipulation.
Maiya
Shubha
S
University of Sheffield, Department of Molecular Biology and Biotechnology, UK.
Grundmann
Alexander
A
Li
Shu-Ming
SM
Turner
Geoffrey
G
D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000235:genetics; D001233:Aspergillus nidulans / Q000235:genetics* / Q000378:metabolism*; D001709:Biotechnology; D015870:Gene Expression; D005818:Genetic Engineering; D026121:Indole Alkaloids / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D010879:Piperazines / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
D026121:Indole Alkaloids; D010879:Piperazines; D011994:Recombinant Proteins; C097859:tryprostatin B