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Haydock SF,
Appleyard AN,
Mironenko T,
Lester J,
Scott N,
Leadlay PF,
( 2005 ) Organization of the biosynthetic gene cluster for the macrolide concanamycin A in Streptomyces neyagawaensis ATCC 27449. PMID : 16207901 : DOI : 10.1099/mic.0.28194-0 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.
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2. |
Labeda DP,
( 2011 ) Multilocus sequence analysis of phytopathogenic species of the genus Streptomyces. PMID : 21112986 : DOI : 10.1099/ijs.0.028514-0 Abstract >>
The identification and classification of species within the genus Streptomyces is difficult because there are presently 576 species with validly published names and this number increases every year. The value of multilocus sequence analysis applied to the systematics of Streptomyces species has been well demonstrated in several recently published papers. In this study the sequence fragments of four housekeeping genes, atpD, recA, rpoB and trpB, were determined for the type strains of 10 known phytopathogenic species of the genus Streptomyces, including Streptomyces scabiei, Streptomyces acidiscabies, Streptomyces europaeiscabiei, Streptomyces luridiscabiei, Streptomyces niveiscabiei, Streptomyces puniciscabiei, Streptomyces reticuliscabiei, Streptomyces stelliscabiei, Streptomyces turgidiscabies and Streptomyces ipomoeae, as well as six uncharacterized phytopathogenic Streptomyces isolates. The type strains of 52 other species, including 19 species observed to be phylogenetically closely related to these, based on 16S rRNA gene sequence analysis, were also included in the study. Phylogenetic analysis of single gene alignments and a concatenated four-gene alignment demonstrated that the phytopathogenic species are taxonomically distinct from each other in spite of high 16S rRNA gene sequence similarities and provided a tool for the identification of unknown putative phytopathogenic Streptomyces strains at the species level.
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