Overproduction of the acyl carrier protein component of a type II polyketide synthase stimulates production of tetracenomycin biosynthetic intermediates in Stteptomyces glaucescens
| Autor: | Heinrich Decker, Richard G. Summers, C. R. Hutchinson |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Pharmacology
Magnetic Resonance Spectroscopy Naphthacenes biology ATP synthase Streptomycetaceae biology.organism_classification Streptomyces Anti-Bacterial Agents chemistry.chemical_compound Acyl carrier protein Polyketide Biosynthesis chemistry Biochemistry Multienzyme Complexes Polyketide synthase Drug Discovery Acyl Carrier Protein biology.protein Overproduction Chromatography High Pressure Liquid Plasmids |
| Zdroj: | The Journal of Antibiotics. 47:54-63 |
| ISSN: | 1881-1469 0021-8820 |
| Popis: | The development of microorganisms with improved antibiotic production is an important goal in the commercialization of new pharmaceuticals or in lowering the cost of established drugs. We report a way to achieve this for biosynthetic intermediates of an antibiotic made by the polyketide pathway whose earliest steps involve a Type II multienzyme complex. Introduction of the tcmKLM beta-ketoacyl: ACP synthase and acyl carrier protein (ACP) genes or just the tcmM ACP gene into the tetracenomycin (Tcm) C-producing Streptomyces glaucescens wild-type strain, or its tcmN or tcmO blocked mutants, on high copy vectors under the control of strong promoters caused a 2 to 30-fold overproduction of Tcm D3 and some other biosynthetic intermediates (or shunt products) and a 25 to 30% increase in Tcm C production relative to the control strains carrying the plasmid vector only. However, Tcm C production was not greater than that obtained with the vector-free wild-type strain. The unexpected effect of increased ACP on Tcm D3 production suggests that the level of this protein can influence either the activity or level of the three other components of the Tcm polyketide synthase. |
| Databáze: | OpenAIRE |
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