Objective
Streptomycetes, or more generally actinomycetes, are versatile and potentially high-yielding producers of proteins and secondary metabolites. Particularly the latter compounds have attracted industrial interest because many secondary metabolites display important pharmacological properties like antibiotic, antiviral, and anti-cancer activity, or have an agricultural application as (animal) feed conversion enhancer or herbicide. A large number of actinomycetes arc currently in use as production organisms in large scale fermentation. However the development of actinomycete production strains and fermentation processes still is highly empirical and therefore unpredictable with respect to both speed and chance of success.
The objective of this project is to integrate fermentation knowledge, metabolic flux analysis, and genetics of substrate utilization and regulatory systems to develop rational strain and process development procedures applicable to a variety of actinomycete strains.
This will be achieved by emphasising general properties of secondary metabolite production: except for the overexpression of secondary metabolites by deregulation of biosynthetic pathway genes, the proposed project will only address basic genetic, biochemical, physiological, and fermentation properties that are conserved within the actinomycete family. This focus ensures that the results will be applicable to strain and process development for a wide variety of actinomycetes.
The results of the project will improve both the effectivity and the efficiency of product formation of new actinomycete industrial processes for secondary metabolites and thus allow fast development of new biologically active products.
Effectivity is defined as the production strain being dedicated to the formation of only one product. The main effort to increase effectivity will comprise creating optimal environmental conditions, physical as well as physiological, to ascertain that the internal metabolism will be directed at the production of a single compound.
Improved effectivity will be achieved through the integration of fermentation studies and analysis of metabolic fluxes, thus establishing which environmental conditions are optimal for secondary metabolite production.
Efficiency is defined as the type and amount of substrate (glucose or oil) that ends up in the final product. Increased efficiency will be achieved by optimization of substrate flux into product by modulation of expression of genes exerting major control over metabolic flux.
In concrete terms the improvements will result in an approximately 25 % reduction of actinomycete strain and process development time, from the screened strain to an economically acceptable production level and in an increase in chance of success by 25 %.
The actinomycete strain to be studied is Streptomyces lividans. The basic strain will resemble an actual production strain with major bottlenecks in metabolite specific biosynthesis already relieved.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics
- natural sciences biological sciences biochemistry biomolecules proteins
- engineering and technology industrial biotechnology bioprocessing technologies fermentation
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2600 MA Delft
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.