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The phaeochromycins from streptomyces strain LL-P018: from taxonomy to novelties of biosynthesis

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TitleInfo
Title
The phaeochromycins from streptomyces strain LL-P018:
from taxonomy to novelties of biosynthesis
Name (type = personal)
NamePart (type = family)
Ritacco
NamePart (type = given)
Frank V.
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Frank Ritacco
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RoleTerm (authority = RUETD)
author
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NamePart (type = family)
Eveleigh
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Douglas
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Advisory Committee
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Douglas E Eveleigh
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chair
Name (type = personal)
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Kukor
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Stanley
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Advisory Committee
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Stanley E Kukor
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internal member
Name (type = personal)
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Kukor
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Jerome
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Advisory Committee
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Jerome J Kukor
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internal member
Name (type = personal)
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Labeda
NamePart (type = given)
David
Affiliation
Advisory Committee
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David P Labeda
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outside member
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School-New Brunswick
Role
RoleTerm (authority = RULIB)
school
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Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2007
DateOther (qualifier = exact); (type = degree)
2007
Language
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English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
xiii, 164 pages
Abstract (type = abstract)
The 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.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject (authority = ETD-LCSH)
Topic
Streptomyces
Subject (authority = ETD-LCSH)
Topic
Bacterial genetics
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.13497
Identifier
ETD_153
Identifier (type = doi)
doi:10.7282/T3W096C0
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
Copyright
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Copyright protected
Availability
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Open
AssociatedEntity (AUTHORITY = rulib); (ID = 1)
Name
Frank Ritacco
Role
Copyright holder
Affiliation
Rutgers University. Graduate School-New Brunswick
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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