Generation of hybrid elloramycin analogs by combinatorial biosynthesis using genes from anthracycline-type and macrolide biosynthetic pathways

Leticia Rodriguez, Carsten Oelkers, Ignacio Aguirrezabalaga, Alfredo F. Braña, Jurgen Rohr, Carmen Méndez, José A. Salas

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Elloramycin and oleandomycin are two polyketide compounds produced by Streptomyces olivaceus Tu2353 and Streptomyces antibioticus ATCC11891, respectively. Elloramycin is an anthracycline-like antitumor drug and oleandomycin a macrolide antibiotic. Expression in S. albus of a cosmid (cos16F4) containing part of the elloramycin biosynthetic gene cluster produced the elloramycin non-glycosylated intermediate 8-demethyl-tetracenomycin C. Several plasmid constructs harboring different gene combinations of L-oleandrose (neutral 2,6-dideoxyhexose attached to the macrolide antibiotic oleandomycin) biosynthetic genes of S. antibioticus that direct the biosynthesis of L-olivose, L-oleandrose and L-rhamnose were coexpressed with cos16F4 in S.albus. Three new hybrid elloramycin analogs were produced by these recombinant strains through combinatorial biosynthesis, containing elloramycinone or 12a-demethyl-elloramycinone (= 8-demethyl-tetracenomycin C) as aglycone moiety encoded by S. olivaceus genes and different sugar moieties, coded by the S. antibioticus genes. Among them is L-olivose, which is here described for the first time as a sugar moiety of a natural product.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalJournal of Molecular Microbiology and Biotechnology
Volume2
Issue number3
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology
  • Applied Microbiology and Biotechnology
  • Molecular Biology

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