Engineering biosynthetic pathways for deoxysugars: Branched-chain sugar pathways and derivatives from the antitumor tetracenomycin

Felipe Lombó, Miranda Gibson, Lisa Greenwell, Alfredo F. Braña, Jürgen Rohr, José A. Salas, Carmen Méndez

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Sugar biosynthesis cassette genes have been used to construct plasmids directing the biosynthesis of branched-chain deoxysugars: pFL942 (NDP-L-mycarose), pFL947 (NDP-4-deacetyl-L-chromose B), and pFL946/pFL954 (NDP-2,3,4-tridemethyl-L-nogalose). Expression of pFL942 and pFL947 in S. lividans 16F4, which harbors genes for elloramycinone biosynthesis and the flexible ElmGT glycosyltransferase of the elloramycin biosynthetic pathway, led to the formation of two compounds: 8-α-L-mycarosyl-elloramycinone and 8-demethyl-8-(4-deacetyl)-α-L-chromosyl-tetracenomycin C, respectively. Expression of pFL946 or pFL954 failed to produce detectable amounts of a novel glycosylated tetracenomycin derivative. Formation of these two compounds represents examples of the sugar cosubstrate flexibility of the ElmGT glycosyltransferase. The use of these cassette plasmids also provided insights into the substrate flexibility of deoxysugar biosynthesis enzymes as the C-methyltransferases EryBIII and MtmC, the epimerases OleL and EryBVII, and the 4-ketoreductases EryBIV and OleU.

Original languageEnglish
Pages (from-to)1709-1718
Number of pages10
JournalChemistry and Biology
Issue number12
StatePublished - Dec 2004

Bibliographical note

Funding Information:
This work was supported by a grant from the Spanish Ministry of Science and Technology to C.M. (BMC2002-03599), a grant from the Plan Regional de Investigación del Principado de Asturias to J.A.S. (GE-MEDO1-05) and an NIH grant (CA 91901 to J.R.). We thank Obra Social Cajastur for financial support to F.L. We thank Pharmamar S.A. for helping in the antitumor tests.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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