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Applied and Environmental Microbiology, May 2007, p. 3412-3422, Vol. 73, No. 10
0099-2240/07/$08.00+0     doi:10.1128/AEM.00129-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Homologue of the Aspergillus velvet Gene Regulates both Cephalosporin C Biosynthesis and Hyphal Fragmentation in Acremonium chrysogenum{triangledown}

Jacqueline Dreyer,1 Heiko Eichhorn,2 Ernst Friedlin,2 Hubert Kürnsteiner,2 and Ulrich Kück1*

Lehrstuhl für Allgemeine und Molekulare Botanik, Ruhr-Universität, Universitätsstr. 150, D-44780 Bochum, Germany,1 Sandoz GmbH, A-6250 Kundl, Austria2

Received 18 January 2007/ Accepted 20 March 2007

The Aspergillus nidulans velvet (veA) gene encodes a global regulator of gene expression controlling sexual development as well as secondary metabolism. We have identified the veA homologue AcveA from Acremonium chrysogenum, the major producer of the ß-lactam antibiotic cephalosporin C. Two different disruption strains as well as the corresponding complements were generated as a prelude to detailed functional analysis. Northern hybridization and quantitative real-time PCR clearly indicate that the nucleus-localized AcVEA polypeptide controls the transcriptional expression of six cephalosporin C biosynthesis genes. The most drastic reduction in expression is seen for cefEF, encoding the deacetoxycephalosporine/deacetylcephalosporine synthetase. After 120 h of growth, the cefEF transcript level is below 15% in both disruption strains compared to the wild type. These transcriptional expression data are consistent with results from a comparative and time-dependent high-performance liquid chromatography analysis of cephalosporin C production. Compared to the recipient, both disruption strains have a cephalosporin C titer that is reduced by 80%. In addition to its role in cephalosporin C biosynthesis, AcveA is involved in the developmentally dependent hyphal fragmentation. In both disruption strains, hyphal fragmentation is already observed after 48 h of growth, whereas in the recipient strain, arthrospores are not even detected before 96 h of growth. Finally, the two mutant strains show hyperbranching of hyphal tips on osmotically nonstabilized media. Our findings will be significant for biotechnical processes that require a defined stage of cellular differentiation for optimal production of secondary metabolites.

* Corresponding author. Mailing address: Lehrstuhl für Allgemeine und Molekulare Botanik, Ruhr-Universität, Universitätsstr. 150, D-44780 Bochum, Germany. Phone: 49-234-3226212. Fax: 49-234-3214184. E-mail: ulrich.kueck{at}ruhr-uni-bochum.de

{triangledown} Published ahead of print on 30 March 2007.

Applied and Environmental Microbiology, May 2007, p. 3412-3422, Vol. 73, No. 10
0099-2240/07/$08.00+0     doi:10.1128/AEM.00129-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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