The mtmVUC genes of the mithramycin gene cluster in Streptomycesargillaceus are involved in the biosynthesis of the sugar moieties View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-02

AUTHORS

A. González, L. L. Remsing, F. Lombó, M. J. Fernández, L. Prado, A. F. Braña, E. Künzel, J. Rohr, C. Méndez, J A. Salas

ABSTRACT

Mithramycin is a glycosylated aromatic polyketide produced by Streptomyces argillaceus, and is used as an antitumor drug. Three genes (mtmV, mtmU and mtmC) from the mithramycin gene cluster have been cloned, and characterized by DNA sequencing and by analysis of the products that accumulate in nonproducing mutants, which were generated by insertional inactivation of these genes. The mtm V gene codes for a 2,3-dehydratase that catalyzes early and common steps in the biosynthesis of the three sugars found in mithramycin (D-olivose, D-oliose and D-mycarose); its inactivation caused the accumulation of the nonglycosylated intermediate premithramycinone. The mtmU gene codes for a 4-ketoreductase involved in D-oliose biosynthesis, and its inactivation resulted in the accumulation of premithramycinone and premithramycin A , the first glycosylated intermediate which contains a D-olivose unit. The third gene, mtmC, is involved in D-mycarose biosynthesis and codes for a C-methyltransferase. Two mutants with lesions in the mtmC gene accumulated mithramycin intermediates lacking the D-mycarose moiety but containing D-olivose units attached to C-12a in which the 4-keto group is unreduced. This suggests that mtmC could code for a second enzyme activity, probably a D-olivose 4-ketoreductase, and that the glycosyltransferase responsible for the incorporation of D-olivose (MtmGIV) shows some degree of flexibility with respect to its sugar co-substrate, since the 4-ketoanalog is also transferred. A pathway is proposed for the biosynthesis of the three sugar moieties in mithramycin. More... »

PAGES

827-835

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s004380000372

DOI

http://dx.doi.org/10.1007/s004380000372

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044372150

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11254130


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