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Discovering Quorum sensing in industrially useful Fungi, a novel approach at molecular level for scaling-up in white biotech

Final Report Summary - QUORUM (Discovering Quorum Sensing in industrially useful Fungi, a novel approach at molecular level for scaling-up in white biotech)

The QUORUM approach has four objectives:
- investigation of fungal quorum sensing for better understanding of biosynthesis of the industrially important target products;
- study of quorum sensing and signal transduction in relation to fungal physiology and morphology in agitated systems;
- comparative analyses of fungal cell communication in small and large scale submerged fermentations;
- exploration of the relevance and interrelation of traditional scale-up factors to quorum sensing in fungal cultures.
The above-mentioned objectives were achieved through joint functional genomics (fungal genomics, transcriptomics, proteomics) and molecular biology, fungal physiology and biochemical engineering investigations.

Here are some of the achievements of the project.

Web based platform for internal and external communication internal and external communication have been performed in different ways: the QUORUM project has its own website, available at the following address: http://www.quorumsensing.eu where contractors may find information, reports, documents, forms and template etc. in the private zone, while a public zone has been provided for general information to the public; the skype and e-mails exchange have shown to be excellent forms of internal communication. For what concerns dissemination, several authorised publications have already been published and many others are planned for the next few months, which have been authorised thanks to the internal approval procedure. For what concerns exploitation, a very useful strategy has been developed in order to motivate partners in identifying the intellectual assets developed through the project and avoid misunderstanding at the end of the project.

In May 2008, project partners attended an exploitation strategy seminar which proved to be extremely useful. After a pre-selection of exploitable knowledge as potential patents and secrets, two patents have been elected where different exploitable knowledge has been included. It was decided to avoid secrets through an inclusion of strategic knowledge in the patents. Other knowledge has been, is being or will be published.

Sensors that are fully applicable in mini- and micro-scale bioreactors were fabricated and tested. Fabrication of the sensors and bioreactor for fermentation and quorum sensing studies and validation of the bioreactor for fermentation have been reached.

Deliverables also include:
- report on a novel sensor for micro bioreactor;
- report on a novel micro-scale bioreactors; and
- report on a novel bioreactor integrating novel sensor have been delivered in due time.

Report on an active QS nano-process in submerged fungal cultures
The objectives of this work package have been to investigate the relation between the physiological state of the fungal cultures in presence of quorum sensing molecules and the levels of the productivity of the target product at different scales of fermentation. To this end we have successfully demonstrated the effect of y-butyrolactones, oxylipins and benzaldehyde in Aspergillus terreus, Aspergillus nidulans and Pleurotus ostreatus respectively on production of secondary metabolites and growth. We have demonstrated that oxylipins isolated from A. nidulans cultures regulate sporulation both in A. nidulans and A. terreus cultures and have a role in lipid based signal transduction. In A. terreus, we have established the role of a potential quorum sensing molecule that affects the production of Iovastatin as well as autoinduces its own production. In Pleurotus ostreatus, we report that benzaldehyde inhibits radial growth and has an effect on many secondary metabolites.

Report on strategy based on QS for potential industrial application
The objective of this work package has also been to establish a novel strategy for production of secondary metabolites at industrial scale employing quorum sensing molecules. Efforts were made in setting up a continuous culture with Aspergillus terreus to establish a strategy for enhanced production of secondary metabolites which will have commercial importance and industrial application. The exogenous addition of known quorum sensing molecules also unravels a potential industrial application whereby the levels of productivity of commercially important metabolites (laccases) were improved in Coriolopsis polyzona. We also reported that exogenous addition of spent medium from Coriolopsis polyzona also has a positive effect on laccase production. Laccase productivity was also improved by supplementing the cultures of Pleurotus ostreatus with the identified QS molecule at 10 L bioreactor level. Butyrolactone I from A. terreus was also investigated for its potential in enhancing Iovastatin production in shaken flask, mid scale bioreactors as well as in continuous culture conditions.