Journal
FUNGAL GENETICS AND BIOLOGY
Volume 46, Issue 5, Pages 436-440Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.fgb.2009.01.003
Keywords
Aspergillus; Secondary metabolism; NRPS; Tryprostatin; Fumitremorgin; Heterologous expression
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Funding
- University of Sheffield
- Deutsche Forschungsgemeinschaft
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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 naive 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. (C) 2009 Elsevier Inc. All rights reserved.
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