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Pathway Description
Tetracycline Biosynthesis
Kitasatospora aureofaciens
Metabolic Pathway
Tetracyclines are aromatic polyketide antibiotics produced via type II polyketide synthases and possess several antibiotic drug properties that work against the activity of Gram-positive and negative bacterial pathogens and are also used to treat several types of bacterial infections in the body. They are natural polyketides produced by actinomycete bacteria like Kitasatospora aureofaciens and are unique by their tetracyclic ring structure and a richly substituted A ring. This pathway shows biosynthesis of naturally occurring tetracyclines (oxytetracycline, tetracycline and chlortetracycline) via the common intermediate anhydrotetracycline. Four genes: oxyE, oxyL, oxyQ, oxyT encode the enzymes that are involved in the modifications that generate anhydrotetracycline. The final two enzymes in the pathway are monooxygenases that are encoded by the gene oxyS and an F420-dependent dehydrogenase encoded by oxyR. OxyS catalyzes two successive monooxygenation reactions where one variation leads to the formation of tetracycline and the other leads to the formation of oxytetracycline. Tetracycline also leads to the formation of chlortetracycline via the enzyme flavin reductase (NADH).
References
Tetracycline Biosynthesis References
Tetracycline Biosynthesis - Kitasatospora aureofaciens. www.kegg.jp/kegg-bin/show_pathway?map=kau00253.
Tetracycline and Oxytetracycline Biosynthesis. biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-7812.
Grossman TH: Tetracycline Antibiotics and Resistance. Cold Spring Harb Perspect Med. 2016 Apr 1;6(4):a025387. doi: 10.1101/cshperspect.a025387.
Pubmed: 26989065
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