title: Genetic engineering of aminodeoxyhexose biosynthesis in Streptomyces fradiae.
abstract: The antibacterial properties of macrolide antibiotics (such as erythromycin, tylosin, and narbomycin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as narbomycin) have only single sugar substituents. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the narbomycin producer Streptomyces narbonensis. This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.
authors.affiliation: Biochemistry Department, University of Leicester, Leicester LE1 7RH, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Butler
authors.forename: Neil
authors.initials: N
authors.lastname: Bate
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Kiehl
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Kirst
authors.forename: Eric
authors.initials: E
authors.lastname: Cundliffe
mesh_terms: D000606:Amino Sugars / Q000096:biosynthesis* / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering / Q000379:methods; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000235:genetics*; D018942:Macrolides / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D014169:Transformation, Bacterial
chemical_list: D000606:Amino Sugars; D018942:Macrolides; C013610:mycaminose; C110125:desosamine; D005944:Glucosamine