Analysis of two chromosomal regions adjacent to genes for a type II polyketide synthase involved in the biosynthesis of the ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-03

AUTHORS

L. Prado, F. Lombó, A. F. Braña, C. Méndez, J. Rohr, J. A. Salas

ABSTRACT

Mithramycin is an aromatic antitumour polyketide synthesized by Streptomyces argillaceus. Two chromosomal regions located upstream and downstream of the locus for the mithramycin type II polyketide synthase were cloned and sequenced. Analysis of the sequence revealed the presence of eight genes encoding three oxygenases (mtmOI, mtmOII and mtmOIII), three reductases (mtmTI, mtmTII and mtmTIII), a cyclase (mtm Y) and an acyl CoA ligase (mtmL). The three oxygenase genes were each inactivated by gene replacement. Inactivation of one of them (mtmOII) generated a non-producing mutant, while inactivation of the other two (mtmOl and mtmOIII) did not affect the biosynthesis of mithramycin. The mtmOII gene may code for an oxygenase responsible for the introduction of oxygen atoms at early steps in the biosynthesis of mithramycin leading to 4-demethylpremithramycinone. One of the reductases may be responsible for reductive cleavage of an intermediate from an enzyme and another for the reduction of a keto group in the side-chain of the mithramycin aglycon moiety. A hypothetical biosynthetic pathway showing in particular the involvement of oxygenase MtmOII and of various other gene products in mithramycin biosynthesis is proposed. More... »

PAGES

216-225

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s004380050960

DOI

http://dx.doi.org/10.1007/s004380050960

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024038018

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10102355


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