Chemical Transformations Encoded by a Streptomyces coelicolor Gene Cluster with an Unusual GTP Cyclohydrolase

Persistent Link:
http://hdl.handle.net/10150/194825
Title:
Chemical Transformations Encoded by a Streptomyces coelicolor Gene Cluster with an Unusual GTP Cyclohydrolase
Author:
Spoonamore, James Edward
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Bacterial secondary metabolite biosynthetic pathways are frequently encoded in gene clusters. Genomic sequence information allows the identification of likely biosynthetic clusters based on sequence homology to known proteins. Biochemical characterization of suspected biosynthetic enzymes affords the discovery of pathways which may never be identified by traditional screening approaches. In the work presented here, I, in some cases in collaboration with others, characterize the three intragenomic GTP cyclohydrolase II (GCH II) homologs from Streptomyces coelicolor A3(2) and show that one catalyzes a related but distinct reaction from the other two. The basis for the altered activity is investigated and speaks to the chemical mechanism of not only the unusual enzyme but also to all GCH II enzymes. Further, I investigate two other enzymes found in the same gene cluster as the unusual GCH II. Using biochemical techniques, I show that the product of the unusual GCH II is used as a substrate by a creatinine amidohydrolase homolog. Using structural biology, I show that the third enzyme, a 6-pyruvoyltetrahydropterin synthase (PTPS), can not catalyze the PTPS reaction but is capable of binding a pterin substrate. Finally, I propose that the cluster from S. coelicolor containing the unusual GCH II encodes enzymes for a novel pathway to produce a pterin.
Type:
text; Electronic Dissertation
Keywords:
Secondary Metabolism; Streptomyces; GTP cyclohydrolase II; Protein Evolution
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Biochemistry & Molecular Biophysics; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Bandarian, Vahe
Committee Chair:
Bandarian, Vahe

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleChemical Transformations Encoded by a Streptomyces coelicolor Gene Cluster with an Unusual GTP Cyclohydrolaseen_US
dc.creatorSpoonamore, James Edwarden_US
dc.contributor.authorSpoonamore, James Edwarden_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractBacterial secondary metabolite biosynthetic pathways are frequently encoded in gene clusters. Genomic sequence information allows the identification of likely biosynthetic clusters based on sequence homology to known proteins. Biochemical characterization of suspected biosynthetic enzymes affords the discovery of pathways which may never be identified by traditional screening approaches. In the work presented here, I, in some cases in collaboration with others, characterize the three intragenomic GTP cyclohydrolase II (GCH II) homologs from Streptomyces coelicolor A3(2) and show that one catalyzes a related but distinct reaction from the other two. The basis for the altered activity is investigated and speaks to the chemical mechanism of not only the unusual enzyme but also to all GCH II enzymes. Further, I investigate two other enzymes found in the same gene cluster as the unusual GCH II. Using biochemical techniques, I show that the product of the unusual GCH II is used as a substrate by a creatinine amidohydrolase homolog. Using structural biology, I show that the third enzyme, a 6-pyruvoyltetrahydropterin synthase (PTPS), can not catalyze the PTPS reaction but is capable of binding a pterin substrate. Finally, I propose that the cluster from S. coelicolor containing the unusual GCH II encodes enzymes for a novel pathway to produce a pterin.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectSecondary Metabolismen_US
dc.subjectStreptomycesen_US
dc.subjectGTP cyclohydrolase IIen_US
dc.subjectProtein Evolutionen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineBiochemistry & Molecular Biophysicsen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBandarian, Vaheen_US
dc.contributor.chairBandarian, Vaheen_US
dc.contributor.committeememberGhosh, Indraneelen_US
dc.contributor.committeememberHorton, Nancyen_US
dc.contributor.committeememberOsterhout, Johnen_US
dc.identifier.proquest2609en_US
dc.identifier.oclc659749600en_US
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