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Uniform 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,
Degree Date2007
Date Created2007
SubjectMicrobiology and Molecular Genetics,
Streptomyces,
Bacterial genetics
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.
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[degree] Ph.D.
Note[NULL] Includes bibliographical references.
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.13497
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.