Activation of silent gene clusters in Aspergillus nidulans

S. Bergmann 1*, V . Schroekh 1, K. Scherlach 2, J. Schuemann 2, H.-W . Nuetzmann 1, C. Hertweck 2,3 and A.A. Brakhage 1,3.

Author address: 

1Department of Molecular and Applied Microbiology and 2Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology -Hans-Knöll-Institute, Jena, Germany. 3Friedrich-Schiller-University, Jena, Germany. s

Abstract: 

Microorganisms as bacteria and fungi produce important low-molecular weight molecules that show different biological activities. Genome mining of available fungal genomes indicated that their potential to produce these compounds designated secondary metabolites (SMs) is greatly underestimated. Fungi encode the genetic information for the biosynthesis of many more compounds which still await discovery. The vast amount of DNA sequence in the public database represents only the beginning of this new genomics era. Most of the fungal secondary metabolism gene clusters are silent under laboratory conditions. Despite this limitation, to get access to the vast number of unknown compounds encoded by silent gene clusters, mixing genomic data, genetic engineering and analytical techniques provides a new avenue to discover novel and potentially bioactive natural products. Bioinformatic analysis of the published A. nidulans genome sequence led to the identification of 48 putative SM gene clusters. By overexpressing a pathway-specific transcription factor, we were able to induce a silent gene cluster containing the gene for a mixed PKS/NRPS system. This approach is rendered feasible by the fact that all of the genes encoding the large number of enzymes required for the synthesis of a typical secondary metabolite are clustered and that in some cases, a single regulator controls the expression of all members of a gene cluster to a certain extent. By this way, we were able to isolate novel compounds. In addition, we will discuss further attempts to activate silent gene clusters and to identify physiological conditions under which gene clusters are active under natural conditions. *Student poster
2009

abstract No: 

41

Full conference title: 

6th International Aspergillus Meeting
    • Asperfest 6 (2009)