Knowledge Based Bio-Economy

MAMBA

New biocatalysts from extreme marine environments

Project Acronym: MAMBA

Title of project: Marine metagenomics for new biotechnological applications

Research area: Biotechnologies (Industrially relevant products and processes from marine biotechnology)

Contract No: 226977

EU Contribution: 2880 000 EURO

Start date: July 2009

Duration: 48 Months

Objectives

The majority of current biotechnological applications are of microbial origin. It is widely appreciated that the microbial world contains by far the greatest fraction of biodiversity in the biosphere. Hence, it can be expected that microbes will provide the greater part of enzyme diversity and the majority of new applications. Marine microbial communities account for more than 80% of life on Earth and have an important role in primary energy and carbon recycling. Hence, marine biochemical and chemo-diversity is considered to be a major target for the discovery of new enzymes and natural products, e.g. for drug development. However, the fact that the majority of these microbes cannot be cultivated limits the application of traditional means of enzyme discovery.

So, this project aims to develop new genomics-based discovery approaches together with the en masse activity characterisation of novel proteins and elucidation of their structures. The organisms used to identify these proteins will be obtained by sampling marine hotspots that cover a wide diversity of microbial life at its limits (hypersaline, low and high temperature, high pressure and low water activity conditions, etc.). Individual enzymes interacting with the substrates of interest will be identified. New proteins will be hyperexpressed, crystallized and their structures elucidated. The most promising candidates will be then scored against chiral substrates of relevance for biocatalysis and their ability to perform in water-free systems will be evaluated.

Then directed evolution will be used to improve the performance and specificity of the enzymes. A comprehensive bioinformatic survey throughout the whole tree of cellular life will be used to reveal and suggest new candidates homologous to the discovered proteins. These proteins from other organisms will be cloned and assayed. The set of new enzymes will be used in biotechnological processes for fine chemical synthesis and drug discovery in association with industrial partners.

Expected Impact

This project will result in rapid characterisation of new metabolic and enzyme activities that can quickly be used to design novel biotech processes and therapeutics. The chosen method of capture of marine genetic information ('activity first') adopted by this project is expected to have a greater impact that the alternative large-scale sequencing of bulk DNA. By concentrating on the functioning of extreme marine microbial consortia the project will make a significant impact in this area since the proteins are more likely to have new characteristics resulting from adaptation to the chosen extreme conditions. It will also impact on many of the obstacles in this field, such as a lack of bioinformatics tailored for the marine field as well as consistent data acquisition and exchange.

The project will also contribute significantly to realizing the vision of a European Research Area (ERA) in the marine sector , in accord with the European Commissions European Strategy for Marine and Maritime Research. A better understanding of the living constituents in the largest ecosystem on earth will help lay the foundation for a wealth of new goods and services of all types through biotechnology. The results from this project will have a strong impact on this goal by taking scientifically validated processes from the research laboratory to the development stage in areas of relevant biotechnology. Subsequent application by companies involved in aspects of fine chemical synthesis will result in greater and more efficient use of natural resources as well as bringing new products to consumers.

Expected Results

Using a new screening platform based on state-of-the-art technologies for archiving, molecular screening, protein structure elucidation, enzyme engineering and directed evolution this project will establish new biotechnical processes (biocatalysis, synthesis of fine chemicals, etc.). It will build up a consortium encompassing state-of-the-art facilities and the expertise required to sample unique and difficult to access marine environments. The use of advanced technology for construction of metagenomic libraries, sequencing, sequence annotation and related bioinformatics resources, as well as high-end activity screening technology, protein crystallization and structural analysis facilities will result in identification and characterisation of new protein based biocatalysts.

These will be utilised by companies with solid market positions in biocatalysis, drug discovery and cosmetics production. The pump-priming of this consortium will deliver a series of new biocatalytic processes, new lead products with anti-tumor activities and new solutes and antioxidant compounds within the project timeframe.

In addition new knowledge will be revealed concerning the metabolic functions of extreme marine microbes and the genomic basis of niche specificities that allow these organisms to thrive in extreme marine environments. It will also indicate the contribution of these microbial consortia to global element cycling and the possible impact of their activities on the global climate patterns.

Website of project:mamba.bangor.ac.uk

Contacts:

Coordinator: Peter Golyshin, p.golyshin@bangor.ac.uk

Organisation: Bangor University, UK, www.bangor.ac.uk

Partners:

Institute for coastal marine environment, Italy, www.cnr.it/istituti/DatiGenerali_eng.html?cds=002

Institute of Catalysis CSIC, Spain, www.icp.csic.es/

Institute of Molecular Enzyme Technology, Heinrich-Heine-University Düsseldorf, Germany, www.iet.uni-duesseldorf.de

Oceanographic Laboratory Banyuls, National Centre for Scientific Research, France, www.obs-banyuls.fr/

French Research Institute for Exploitation of the Sea, France, www.ifremer.fr/anglais/

Research Institute Pierre Fabre, France, www.pierre-fabre.com

University of Toronto, Canada, www.uhnresearch.ca/centres/proteomics/

Argonne National Laboratory, USA,

Max Planck Institute for Marine Microbiology, Germany, www.mpi-bremen.de/

Pharma Mar S.A. Spain, www.pharmamar.com/

Evocatal GmbH, Germany, www.evocatal.com/