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AIR2-CT94-0967
Manipulation of Lipid Metabolism Aimed at Production of Fatty Acids and Polyketides for Industrial Use and for Application in Functional Foods |
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Contract No | AIR2-CT94-0967 |
| Total Cost | 3 004 540 ECU | |
| EC Contribution | 1 769 770 ECU | |
| Start Date | 01/09/1994 | |
| Duration | 50 months |
SUMMARY
All living organisms contain lipids, more generally known as fats. These consist of long chain fatty acids esterified to glycerol and in some cases to sugars, amino acids, phosphate, sulphate and other similar molecules. However, wide differences are seen between the fatty acids found in various organisms. They may differ in terms of their chain length (number of carbon atoms), degree of saturation (number and position of double bonds) and inclusion of unusual stereochemical configurations or chemical groups, such as epoxides. This project aims to build a better understanding of lipid metabolism in order to develop methods of enhancing the production of desirable compounds.
OBJECTIVE
In eukaryotic micro-organisms and plants, acetyl-CoA is a precursor for the synthesis of many compounds including fatty acids and polyketides. Apart from the value of these compounds to the cells in which they are synthesized, the fatty acids find increasing application in the food and chemical industries. Some polyketides on the other hand are food-associated toxins, whereas others are widely used as antibiotics and pharmaceuticals. The fatty acid synthase (FAS) and polyketide synthase (PKS) enzymes are remarkably similar in their function with differences apparent primarily in the detailed programming. These two enzymes constitute a metabolic branch point between primary and secondary metabolism. Fatty acids enter a second branch point between membrane lipid biosynthesis (functional fats) and fat accumulation (storage fats) and this switch is controlled by the acyl-CoA; diacylglycerol transferase (DAGAT) enzyme. This proposal describes a highly coordinated and inter-dependent research programme to investigate metabolic switching and pathway manipulation in yeasts, filamentous fungi and plants which focuses on the production of fatty acids and polyketides. Research effort is concentrated on FAS, PKS, DAGAT, supply of acetyl-CoA and the ability to produce fatty acids of predetermined chain length and degree of desaturation. Target species have been chosen because of their detailed genetic history (Saccharomyces cerevisiae, Aspergillus nidulans and Brassica napus), their ability to accumulate fats/oils (Apiotrichum curvatum and Brassica napus) and moulds which are important in food biotechnology (Aspergillus niger). The programme has brought together six participating laboratories in three countries with expertise in enzymology, biochemistry, physiology and molecular biology relating to the central thrust of the research. By combining the strength of each laboratory the programme aims to be able to programme yeast, moulds and plants for production of particular (including novel) fatty acids and polyketides in required amounts. Realization of this objective necessitates improved understanding of the relevant metabolism, pathway manipulation and flux control.
Publications from the project include
Adams, I.P., Dack, S., Dickinson, F.M., Midgley, M., Ratledge, C. (1997). ATP: Citrate lyase from Aspergillus nidulans. Biochemical Society Transactions 25: S670
Dahlqvist, A. and Stymne, S. (1997). Regulation of lipid synthesising enzymes by the lipid environment. National Plant Lipid Cooperative Symposium, Lake Tahoe, California.
Meesters, P.A.E.P., Springer, J. and Eggink, G. (1997) Cloning and expression of the fatty acid desaturase gene from Cryptococcus curvatus ATCC 20509. Applied Microbiology and Biotechnology 47: 663-667.
Morrice, J., MacKenzie, D.A., Parr, A.J. and Archer, D.B. (1997) Isolation and characterisation of two putative acetyl-CoA carboxylase genes and their role in sterigmatocystin production in Aspergillus nidulans. Proceedings of the British Mycological Society and FEMS European Conference on Fungal Physiology and Biochemistry, Nottingham, U.K., April, abstract P42.
Morrice, J., MacKenzie, D.A., Parr, A.J. and Archer, D.B. (1997) Isolation and characterisation of two putative acetyl-CoA carboxylase genes and their role in sterigmatocystin production in Aspergillus nidulans. Proceedings of the European Research Conference on the Control of Metabolic Flux, Giens, France, June, abstract p.47
Contacts
Coordinator
EC Scientific Officer
Participant
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