Mironenko T

References (4)

Title : Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338 - Oliynyk_2007_Nat.Biotechnol_25_447
Author(s) : Oliynyk M , Samborskyy M , Lester JB , Mironenko T , Scott N , Dickens S , Haydock SF , Leadlay PF
Ref : Nat Biotechnol , 25 :447 , 2007
Abstract : Saccharopolyspora erythraea is used for the industrial-scale production of the antibiotic erythromycin A, derivatives of which play a vital role in medicine. The sequenced chromosome of this soil bacterium comprises 8,212,805 base pairs, predicted to encode 7,264 genes. It is circular, like those of the pathogenic actinomycetes Mycobacterium tuberculosis and Corynebacterium diphtheriae, but unlike the linear chromosomes of the model actinomycete Streptomyces coelicolor A3(2) and the closely related Streptomyces avermitilis. The S. erythraea genome contains at least 25 gene clusters for production of known or predicted secondary metabolites, at least 72 genes predicted to confer resistance to a range of common antibiotic classes and many sets of duplicated genes to support its saprophytic lifestyle. The availability of the genome sequence of S. erythraea will improve insight into its biology and facilitate rational development of strains to generate high-titer producers of clinically important antibiotics.
ESTHER : Oliynyk_2007_Nat.Biotechnol_25_447
PubMedSearch : Oliynyk_2007_Nat.Biotechnol_25_447
PubMedID: 17369815
Gene_locus related to this paper: sacen-a4f6m6 , sacen-a4f7j2 , sacen-a4f7j9 , sacen-a4f8h3 , sacen-a4f8m4 , sacen-a4f8u9 , sacen-a4f9g1 , sacen-a4f9k7 , sacen-a4f815 , sacen-a4f824 , sacen-a4fam2 , sacen-a4faz0 , sacen-a4fbh5 , sacen-a4fbt1 , sacen-a4fc70 , sacen-a4fc79 , sacen-a4fcc3 , sacen-a4fcq9 , sacen-a4fcs3 , sacen-a4fd56 , sacen-a4fdc0 , sacen-a4fdk1 , sacen-a4fdp9 , sacen-a4fdt6 , sacen-a4fdt8 , sacen-a4feu5 , sacen-a4few8 , sacen-a4ff15 , sacen-a4ffg0 , sacen-a4ffk3 , sacen-a4ffv6 , sacen-a4ffx1 , sacen-a4ffy1 , sacen-a4fgk3 , sacen-a4fgw0 , sacen-a4fh60 , sacen-a4fix9 , sacen-a4fiz9 , sacen-a4fja4 , sacen-a4fjd3 , sacen-a4fk07 , sacen-a4fk92 , sacen-a4fkg4 , sacen-a4fkn0 , sacen-a4flt0 , sacen-a4fmr1 , sacen-a4fmz0 , sacen-a4fn55 , sacen-a4fpb3 , sacen-a4fpf4 , sacen-a4fpp0 , sacen-a4fq24 , sacer-Q9JN61 , sacen-a4fnh7 , sacen-a4fd61 , sacen-a4ffa2

Title : Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137 - Harvey_2007_Chem.Biol_14_703
Author(s) : Harvey BM , Mironenko T , Sun Y , Hong H , Deng Z , Leadlay PF , Weissman KJ , Haydock SF
Ref : Chemical Biology , 14 :703 , 2007
Abstract : Nigericin was among the first polyether ionophores to be discovered, but its biosynthesis remains obscure. The biosynthetic gene cluster for nigericin has been serendipitously cloned from Streptomyces sp. DSM4137, and deletion of this gene cluster abolished the production of both nigericin and the closely related metabolite abierixin. Detailed comparison of the nigericin biosynthetic genes with their counterparts in the biosynthetic clusters for other polyketides has prompted a significant revision of the proposed common pathway for polyether biosynthesis. In particular, we present evidence that in nigericin, nanchangmycin, and monensin, an unusual ketosynthase-like protein, KSX, transfers the initially formed linear polyketide chain to a discrete acyl carrier protein, ACPX, for oxidative cyclization. Consistent with this, deletion of either monACPX or monKSX from the monensin gene cluster effectively abolished monensin A biosynthesis.
ESTHER : Harvey_2007_Chem.Biol_14_703
PubMedSearch : Harvey_2007_Chem.Biol_14_703
PubMedID: 17584617
Gene_locus related to this paper: strvo-q27w67

Title : Organization of the biosynthetic gene cluster for the macrolide concanamycin A in Streptomyces neyagawaensis ATCC 27449 - Haydock_2005_Microbiology_151_3161
Author(s) : Haydock SF , Appleyard AN , Mironenko T , Lester J , Scott N , Leadlay PF
Ref : Microbiology , 151 :3161 , 2005
Abstract : The macrolide antibiotic concanamycin A has been identified as an exceptionally potent inhibitor of the vacuolar (V-type) ATPase. Such compounds have been mooted as the basis of a potential drug treatment for osteoporosis, since the V-ATPase is involved in the osteoclast-mediated bone resorption that underlies this common condition. To enable combinatorial engineering of altered concanamycins, the biosynthetic gene cluster governing the biosynthesis of concanamycin A has been cloned from Streptomyces neyagawaensis and shown to span a region of over 100 kbp of contiguous DNA. An efficient transformation system has been developed for S. neyagawaensis and used to demonstrate the role of the cloned locus in the formation of concanamycin A. Sequence analysis of the 28 ORFs in the region has revealed key features of the biosynthetic pathway, in particular the biosynthetic origin of portions of the backbone, which arise from the unusual polyketide building blocks ethylmalonyl-CoA and methoxymalonyl-ACP, and the origin of the pendant deoxysugar moiety 4'-O-carbamoyl-2'-deoxyrhamnose, as well as the presence of a modular polyketide synthase (PKS) encoded by six giant ORFs. Examination of the methoxymalonyl-specific acyltransferase (AT) domains has led to recognition of an amino acid sequence motif which can be used to distinguish methylmalonyl-CoA- from methoxymalonyl-ACP-specific AT domains in natural PKSs.
ESTHER : Haydock_2005_Microbiology_151_3161
PubMedSearch : Haydock_2005_Microbiology_151_3161
PubMedID: 16207901
Gene_locus related to this paper: 9acto-q3s868 , 9acto-q3s880

Title : Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase - Li_2004_Chem.Biol_11_107
Author(s) : Li TL , Huang F , Haydock SF , Mironenko T , Leadlay PF , Spencer JB
Ref : Chemical Biology , 11 :107 , 2004
Abstract : The gene cluster encoding biosynthesis of the clinically important glycopeptide antibiotic teicoplanin has been cloned from Actinoplanes teichomyceticus. Forty-nine putative open reading frames (ORFs) were identified within an 89 kbp genetic locus and assigned roles in teicoplanin biosynthesis, export, resistance, and regulation. Two ORFs, designated orfs 1 and 10*, showed significant homology to known glycosyltransferases. When heterologously expressed in Escherichia coli, these glycosyltransferases were shown to catalyze the transfer of UDP-(N-acetyl)-glucosamine onto, respectively, 3-chloro-beta-hydroxytyrosine-6 (3-Cl-6betaHty) and 4-hydroxyphenylglycine-4 (4Hpg) of the teicoplanin heptapeptide aglycone. The product of another ORF, orf11*, was demonstrated in vitro to transfer n-acetyl-, n-butyryl-, and n-octanoyl-groups from acyl-CoA donors either to a free UDP-aminosugar or to an aminosugar moiety in the teicoplanin pseudoaglycone, thus identifying Orf11* as the key acyltransferase in teicoplanin maturation. These findings should accelerate the combinatorial engineering of new and improved glycopeptide drugs.
ESTHER : Li_2004_Chem.Biol_11_107
PubMedSearch : Li_2004_Chem.Biol_11_107
PubMedID: 15113000
Gene_locus related to this paper: actti-q6zzg3 , actti-q6zzj3 , actti-q6zzg0