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The phaeochromycins from streptomyces strain LL-P018: from taxonomy to novelties of biosynthesis
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Ritacco, Frank V.. The phaeochromycins from streptomyces strain LL-P018: from taxonomy to novelties of biosynthesis. Retrieved from https://doi.org/doi:10.7282/T3W096C0

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TitleThe phaeochromycins from streptomyces strain LL-P018:
from taxonomy to novelties of biosynthesis
NameRitacco, Frank V. (author); Eveleigh, Douglas (chair); Kukor, Stanley (internal member); Kukor, Jerome (internal member); Labeda, David (outside member); Rutgers University; Graduate School-New Brunswick
Date Created2007
Other Date2007 (degree)
SubjectMicrobiology and Molecular Genetics, Streptomyces, Bacterial genetics
Extentxiii, 164 pages
DescriptionThe phaeochromycins are a newly discovered family of aromatic polyketides produced by Streptomyces strain LL-P018. The novel phaeochromycins A and C are of medical interest as they have inhibitory activity against MK-2, a kinase involved in the inflammatory response. The phaeochromycins are structurally similar to actinomycete secondary shunt metabolites derived from the actinorhodin and enterocin biosynthetic pathways. Because these phaeochromycins show promise as potential anti-inflammatory therapeutic agents, further knowledge of their biosynthesis and the taxonomy of the producing organism was sought. Strain LL-P018 was identified taxonomically using a combination of traditional and molecular techniques. Analyses of morphology, physiology, 16S ribosomal RNA (16SrRNA) sequence, and ribosomal polymerase β- subunit (rpoB) gene sequence were used to identify LL-P018 as a strain of Streptomyces phaeochromogenes. New methods for strain comparison by combining genetic fingerprints and metabolite profiles in a single comparison were developed to assess strain variation between strain LL-P018 and closely related organisms. This approach also clarified relationships between multiple "types" and other published strains of S. phaeochromogenes and Streptomyces ederensis. Alnumycin, an additional aromatic polyketide which has structural similarities to the phaeochromycins, was produced by strain LL-P018 in liquid culture media. Genomic analysis of strain LL-P018 revealed the presence of a type II polyketide synthase gene cluster. Gene disruption experiments determined this pathway to be responsible for both phaeochromycin and alnumycin biosynthesis, suggesting that the phaeochromycins may be intermediates or shunt products in alnumycin biosynthesis.
This thesis describes a novel taxonomic approach to classification which integrates data from prior genetic and metabolic assessments into a single combined comparison. The S. phaeochromogenes type strain is defined, and taxonomic status of the species S. ederensis is clarified. New insights of phaeochromycin biosynthesis are revealed by cultural and genetic studies of Streptomyces strain LL-P018.
NotePh.D.
NoteIncludes bibliographical references.
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3W096C0
LanguageEnglish
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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