ISSN:
1476-5535
Schlagwort(e):
Hybrid antibiotics
;
Polyketide biosynthesis
;
Anthracyclines
;
Actinorhodin
;
Streptomycetes
;
Interspecies gene cloning
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Biologie
,
Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
Notizen:
Summary There are now several examples showing that hybrid secondary metabolites can be produced as a result of interspecies cloning of antibiotic biosynthesis genes in streptomycetes. This paper reviews examples of hybrid secondary metabolite production, and examines the underlying biochemical and regulatory principles leading to the formation of hybrid anthraquinones by recombinant anthracycline-producing streptomycetes carrying actinorhodin biosynthesis genes. An anthraquinone, aloesaponarin II, was produced by cloning theactI, actIII, actIV, andactVII genes (pANT12) of actinorhodin biosynthesis pathway fromStreptomyces coelicolor in anthracycline producing streptomycetes.Streptomyces galilaeus strains 31 133 and 31 671, aclacinomycin and 2-hydroxyaklavinone producers, respectively, formed aloesaponarin II as their major polyketide product when transformed with pANT12. Subcloning experiments indicated that a 2.8-kbXhoI fragment containing only theactI andactVII loci was necessary for aloesaponarin II biosynthesis byS. galilaeus 31 133. WhenS. galilaeus 31 671 was transformed with theactI, actVII, andactIV genes, however, the recombinant strain produced two novel anthraquinones, desoxyerythrolaccin and 1-0-methyldesoxyerythrolaccin. WhenS. galilaeus 31671 was transformed with only the intactactIII gene (pANT45), aklavinone was formed exclusively. These experiments indicate a function for theactIII gene, which is the reduction of the keto group at C-9 from the carboxyl terminus of the assembled polyketide to the corresponding secondary alcohol. The effects of three regulatory loci,dauG, dnrR1, andasaA, on the production of natural and hybrid polyketides were also shown.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF01575879
Permalink
