Aspergillus as a multi-purpose cell factory: current status and perspectives

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Abstract

Aspergilli have a long history in biotechnology as expression platforms for the production of food ingredients, pharmaceuticals and enzymes. The achievements made during the last years, however, have the potential to revolutionize Aspergillus biotechnology and to assure Aspergillus a dominant place among microbial cell factories. This mini-review will highlight most recent breakthroughs in fundamental and applied Aspergillus research with a focus on new molecular tools, techniques and products. New trends and concepts related to Aspergillus genomics and systems biology will be discussed as well as the challenges that have to be met to integrate omics data with metabolic engineering attempts.

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Most cited references 47

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SMURF: Genomic mapping of fungal secondary metabolite clusters.

Nora Khaldi, Fayaz Seifuddin, Geoff Turner … (2010)

Fungi produce an impressive array of secondary metabolites (SMs) including mycotoxins, antibiotics and pharmaceuticals. The genes responsible for their biosynthesis, export, and transcriptional regulation are often found in contiguous gene clusters. To facilitate annotation of these clusters in sequenced fungal genomes, we developed the web-based software SMURF (www.jcvi.org/smurf/) to systematically predict clustered SM genes based on their genomic context and domain content. We applied SMURF to catalog putative clusters in 27 publicly available fungal genomes. Comparison with genetically characterized clusters from six fungal species showed that SMURF accurately recovered all clusters and detected additional potential clusters. Subsequent comparative analysis revealed the striking biosynthetic capacity and variability of the fungal SM pathways and the correlation between unicellularity and the absence of SMs. Further genetics studies are needed to experimentally confirm these clusters. 2010 Elsevier Inc. All rights reserved.

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Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans.

Volker Schroeckh, Kirstin Scherlach, Hans-Wilhelm Nützmann … (2009)

Fungi produce numerous low molecular weight molecules endowed with a multitude of biological activities. However, mining the full-genome sequences of fungi indicates that their potential to produce secondary metabolites is greatly underestimated. Because most of the biosynthesis gene clusters are silent under laboratory conditions, one of the major challenges is to understand the physiological conditions under which these genes are activated. Thus, we cocultivated the important model fungus Aspergillus nidulans with a collection of 58 soil-dwelling actinomycetes. By microarray analyses of both Aspergillus secondary metabolism and full-genome arrays and Northern blot and quantitative RT-PCR analyses, we demonstrate at the molecular level that a distinct fungal-bacterial interaction leads to the specific activation of fungal secondary metabolism genes. Most surprisingly, dialysis experiments and electron microscopy indicated that an intimate physical interaction of the bacterial and fungal mycelia is required to elicit the specific response. Gene knockout experiments provided evidence that one induced gene cluster codes for the long-sought after polyketide synthase (PKS) required for the biosynthesis of the archetypal polyketide orsellinic acid, the typical lichen metabolite lecanoric acid, and the cathepsin K inhibitors F-9775A and F-9775B. A phylogenetic analysis demonstrates that orthologs of this PKS are widespread in nature in all major fungal groups, including mycobionts of lichens. These results provide evidence of specific interaction among microorganisms belonging to different domains and support the hypothesis that not only diffusible signals but intimate physical interactions contribute to the communication among microorganisms and induction of otherwise silent biosynthesis genes.

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Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans.

Sebastian Bergmann, Julia Schumann, Kirstin Scherlach … (2007)

In the postgenomic era it has become increasingly apparent that the vast number of predicted biosynthesis genes of microorganisms is not reflected by the metabolic profile observed under standard fermentation conditions. In the absence of a particular (in most cases unknown) trigger these gene loci remain silent. Because these cryptic gene clusters may code for the biosynthesis of important virulence factors, toxins, or even drug candidates, new strategies for their activation are urgently needed to make use of this largely untapped reservoir of potentially bioactive compounds. The discovery of new microbial metabolites through genome mining has proven to be a very promising approach. Even so, the investigation of silent gene clusters is still a substantial challenge, particularly in fungi. Here we report a new strategy for the successful induction of a silent metabolic pathway in the important model organism Aspergillus nidulans, which led to the discovery of novel PKS-NRPS hybrid metabolites.

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Author and article information

Contributors

: +31-71-5275056 , +31-71-5274999 , v.meyer@biology.leidenuniv.nl

Journal

Journal ID (nlm-ta): Biotechnol Lett

Title: Biotechnology Letters

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 0141-5492

ISSN (Electronic): 1573-6776

Publication date (Electronic): 19 November 2010

Publication date PMC-release: 19 November 2010

Publication date (Print): March 2011

Volume: 33

Issue: 3

Pages: 469-476

Affiliations

[1 ]Department of Molecular Microbiology and Biotechnology, Leiden University, Institute of Biology Leiden, Sylviusweg 72, 2333 BE Leiden, The Netherlands

[2 ]The Netherlands & Kluyver Centre for Genomics of Industrial Fermentation, P.O. Box 5057, 2600 GA Delft, The Netherlands

[3 ]Sichuan University, College of Life Sciences, Sichuan Key Laboratory for Molecular Biology and Biotechnology, Wangjiang Rd 29, Chengdu, 610064 China

Article

Publisher ID: 473

DOI: 10.1007/s10529-010-0473-8

PMC ID: 3040820

PubMed ID: 21088867

SO-VID: 650e9e33-e366-49f1-95a9-90dcf6db5a76

History

Date received : 21 October 2010

Date accepted : 29 October 2010

Custom metadata

ScienceOpen disciplines: Biotechnology

Keywords: genomics,aspergillus,organelle engineering,genetic engineering,systems biology,expression platform

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ScienceOpen disciplines: Biotechnology

Keywords: genomics, aspergillus, organelle engineering, genetic engineering, systems biology, expression platform

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