Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus

  title={Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus},
  author={Luis M. Quir{\'o}s and Ignacio Aguirrezabalaga and Carlos Olano and Carmen M{\'e}ndez and Jos{\'e} A Salas},
  journal={Molecular Microbiology},
A 5.2 kb region from the oleandomycin gene cluster in Streptomyces antibioticus located between the oleandomycin polyketide synthase gene and sugar biosynthetic genes was cloned. Sequence analysis revealed the presence of three open reading frames (designated oleI, oleN2 and oleR). The oleI gene product resembled glycosyltransferases involved in macrolide inactivation including the oleD product, a previously described glycosyltransferase from S. antibioticus. The oleN2 gene product showed… 

Identification and Expression of Genes Involved in Biosynthesis of L-Oleandrose and Its Intermediate L-Olivose in the Oleandomycin Producer Streptomyces antibioticus

A 9.8-kb DNA region from the oleandomycin gene cluster in Streptomyces antibioticus was cloned and it was revealed that pOLV and pOLE encode all enzyme activities required for the biosynthesis of these two 2,6dideoxysugars.

Cloning, characterization and heterologous expression of a polyketide synthase and P-450 oxidase involved in the biosynthesis of the antibiotic oleandomycin.

The heterologous expression system reported here provides a useful tool for studying this important macrolide antibiotic and indicates that OleP is involved in the epoxidation pathway of oleandomycin biosynthesis.

Functional Analysis of OleY l-Oleandrosyl 3-O-Methyltransferase of the Oleandomycin Biosynthetic Pathway in Streptomyces antibioticus

Oleandomycin, a macrolide antibiotic produced by Streptomyces antibioticus, contains two sugars attached to the aglycon: L-oleandrose and D-desosamine, which represents an alternative route for L-olesandrose biosynthesis from that in the avermectin producer StrePTomyces avermitilis.

Interspecies complementation in Saccharopolyspora erythraea : elucidation of the function of oleP1, oleG1 and oleG2 from the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus and generation of new erythromycin derivatives

Interspecies complementation has been carried out, using two mutant strains of Saccharopolyspora erythraea to identify which of these two glycosyltransferases encodes the desosaminyltransferase and which the oleandrosyltransferase, and to demonstrate that the function of OleP1 is identical to that of EryCII in the biosynthesis of dTDP‐d‐desosamine.

Glycosylation Steps during Spiramycin Biosynthesis in Streptomyces ambofaciens: Involvement of Three Glycosyltransferases and Their Interplay with Two Auxiliary Proteins

Analysis of the biosynthetic intermediates accumulated by mutant strains devoid of each of the auxiliary proteins, together with complementation experiments, revealed the interplay of glycosyltransferases with the Auxiliary proteins.

Identification of Two Genes from Streptomyces argillaceus Encoding Glycosyltransferases Involved in Transfer of a Disaccharide during Biosynthesis of the Antitumor Drug Mithramycin

It is proposed that the glycosyltransferases encoded by mtmGI and mtmGII are responsible for forming and transferring the disaccharide during mithramycin biosynthesis.

Glycosylation of Macrolide Antibiotics

The oleD gene has been identified in the oleandomycin producer Streptomyces antibioticus and it codes a macrolide glycosyltransferase that is able to transfer a glucose moiety from UDP-glucose

Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus

It is demonstrated that the glycosyltransferases MtmGIV and mtmGIII catalyze the first two glycosolation steps in mithramycin biosynthesis.



A second ABC transporter is involved in oleandomycin resistance and its secretion by Streptomyces antibioticus

Functional analysis of the oleB gene showed that either the first or the second half of the gene containing only one ATP‐binding domain was sufficient to confer resistance to oleandomycin, and it was shown that a Streptomyces albus strain, containing both a glycosyltransferase and the OleB protein, was capable ofglycosylating ole fandomycin and secreting the inactive Glycosylated molecule.

Streptomyces antibioticus contains at least three oleandomycin‐resistance determinants, one of which shows similarity with proteins of the ABC‐transporter superfamily

The results suggest that resistance to oleandomycin conferred by oleC (orf4) is probably due to an efflux transport system of the ABC‐transporter superfamily.

Role of glycosylation and deglycosylation in biosynthesis of and resistance to oleandomycin in the producer organism, Streptomyces antibioticus.

Interestingly, the culture supernatant contains another enzyme activity capable of reactivating the glycosylated oleandomycin and regenerating the biological activity through the release of a glucose molecule, and it is proposed that these two enzyme activities could be an integral part of the ole fandomycin biosynthetic pathway.

Interaction between ATP, oleandomycin and the OleB ATP-binding cassette transporter of Streptomyces antibioticus involved in oleandomycin secretion.

Significant changes in the intrinsic fluorescence of the fusion protein were also observed in the presence of OM, demonstrating the existence of interaction between the transporter and the antibiotic in the absence of any hydrophobic membrane component.

Microbial glycosylation of macrolide antibiotics by Streptomyces hygroscopicus ATCC 31080 and distribution of a macrolide glycosyl transferase in several Streptomyces strains.

Examination of 32 actinomycete strains producing such polyketides as macrolide and polyether antibiotics, and found that 15 strains of Streptomyces have macrolides glycosyl transferase activity, suggests that the MGTs have been distributed among at least polyketide producing StrePTomyces strains.

Biosynthesis of the Macrolide Oleandomycin by Streptomyces antibioticus

The oleandomycin producer, Streptomyces antibioticus, possesses a mechanism involving two enzymes for the intracellular inactivation and extracellular reactivation of the antibiotic, which has been shown to operate via a compulsory-order mechanism.

Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis

The eryC1‐gene product, a protein of subunit Mr 39200, is therefore involved either as a structural or as a regulatory gene in the formation of the deoxyamino‐sugar desosamine or in its attachment to the macro‐lide ring.

Resistance to oleandomycin in Streptomyces antibioticus, the producer organism.

While S. albus G took up oleandomycin, S. antibioticus showed a decreased permeability to the antibiotic, suggesting a role for cell permeability in self-resistance.

Analysis of seven genes from the eryAI –eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea

R roles are proposed for several of these ORFs in the biosynthesis of the deoxysugar mycarose and the deoxyaminosugar desosamine in the macrolide antibiotic erythromycin A by Saccharopolyspora erystraea.