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Biosynthesis of trioxacarcin revealing a different starter unit and complex tailoring steps for type II polyketide synthase
- Source :
- Chemical Science
- Publication Year :
- 2015
- Publisher :
- Royal Society of Chemistry (RSC), 2015.
-
Abstract
- Different starter unit and complex tailoring steps for type II polyketide synthase in trioxacarcin biosynthesis.<br />Trioxacarcins (TXNs) are highly oxygenated, polycyclic aromatic natural products with remarkable biological activity and structural complexity. Evidence from 13C-labelled precursor feeding studies demonstrated that the scaffold was biosynthesized from one unit of l-isoleucine and nine units of malonyl-CoA, which suggested a different starter unit in the biosynthesis. Genetic analysis of the biosynthetic gene cluster revealed 56 genes encoding a type II polyketide synthase (PKS), combined with a large amount of tailoring enzymes. Inactivation of seven post-PKS modification enzymes resulted in the production of a series of new TXN analogues, intermediates, and shunt products, most of which show high anti-cancer activity. Structural elucidation of these new compounds not only helps us to propose the biosynthetic pathway, featuring a type II PKS using a novel starter unit, but also set the stage for further characterization of the enzymatic reactions and combinatorial biosynthesis.
- Subjects :
- chemistry.chemical_classification
biology
Stereochemistry
technology, industry, and agriculture
food and beverages
Biological activity
General Chemistry
Enzyme catalysis
Chemistry
chemistry.chemical_compound
Enzyme
Starter
chemistry
Biosynthesis
Biochemistry
Polyketide synthase
Gene cluster
biology.protein
bacteria
Gene
Subjects
Details
- ISSN :
- 20416539 and 20416520
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Chemical Science
- Accession number :
- edsair.doi.dedup.....3f436a93bf0995d4d2860a7dc20004d3