Improving production of bioactive secondary metabolites in actinomycetes by metabolic engineering

Production of secondary metabolites is a process influenced by several physico-chemical factors including nutrient supply, oxygenation, temperature and pH. These factors have been traditionally controlled and optimized in industrial fermentations in order to enhance metabolite production. In additio...

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Bibliographic Details
Published in:Metabolic engineering 2008-09, Vol.10 (5), p.281-292
Main Authors: Olano, Carlos, Lombó, Felipe, Méndez, Carmen, Salas, José A.
Format: Article
Language:English
Subjects:
Actinomyces - drug effects
Actinomyces - genetics
Actinomyces - metabolism
Antibiotic biosynthesis
Genetic Engineering - methods
Genome shuffling
Heterologous expression
Metabolism
Precursor engineering
Regulation
Ribosome engineering
Streptomyces
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Summary:Production of secondary metabolites is a process influenced by several physico-chemical factors including nutrient supply, oxygenation, temperature and pH. These factors have been traditionally controlled and optimized in industrial fermentations in order to enhance metabolite production. In addition, traditional mutagenesis programs have been used by the pharmaceutical industry for strain and production yield improvement. In the last years, the development of recombinant DNA technology has provided new tools for approaching yields improvement by means of genetic manipulation of biosynthetic pathways. These efforts are usually focused in redirecting precursor metabolic fluxes, deregulation of biosynthetic pathways and overexpression of specific enzymes involved in metabolic bottlenecks. In addition, efforts have been made for the heterologous expression of biosynthetic gene clusters in other organisms, looking not only for an increase of production levels but also to speed the process by using rapidly growing and easy to manipulate organisms compared to the producing organism. In this review, we will focus on these genetic approaches as applied to bioactive secondary metabolites produced by actinomycetes.
ISSN:1096-7176
1096-7184
DOI:10.1016/j.ymben.2008.07.001