Affiliation:
1. Lehrstuhl für Allgemeine und Molekulare Botanik, Ruhr-Universität, Universitätsstr. 150, D-44780 Bochum, Germany
2. Sandoz GmbH, A-6250 Kundl, Austria
Abstract
ABSTRACT
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 Ac
veA
from
Acremonium chrysogenum
, the major producer of the β-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, Ac
veA
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.
Publisher
American Society for Microbiology
Subject
Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology
Reference49 articles.
1. Bartoshevich, Y. E., P. L. Zaslavskaya, M. J. Novak, and O. D. Yudina. 1990. Acremonium chrysogenum differentiation and biosynthesis of cephalosporin. J. Basic Microbiol.30:313-320.
2. Beals, C. R., N. A. Clipstone, S. N. Ho, and G. R. Crabtree. 1997. Nuclear localization of NF-ATc by a calcineurin-dependent, cyclosporin-sensitive intramolecular interaction. Genes Dev.11:824-834.
3. Blumenstein, A., K. Vienken, R. Tasler, J. Purschwitz, D. Veith, N. Frankenberg-Dinkel, and R. Fischer. 2005. The Aspergillus nidulans phytochrome FphA represses sexual development in red light. Curr. Biol.15:1833-1838.
4. Brakhage, A. A., Q. Al-Abdallah, A. Tuncher, and P. Spröte. 2005. Evolution of beta-lactam biosynthesis genes and recruitment of trans-acting factors. Phytochemistry66:1200-1210.
5. Brakhage, A. A., P. Spröte, Q. Al-Abdallah, A. Gehrke, H. Plattner, and A. Tuncher. 2004. Regulation of penicillin biosynthesis in filamentous fungi. Adv. Biochem. Eng. Biotechnol.88:45-90.
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