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Biosynthetic Strategies for Chemodiv...
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Moss, Nathan Aaron.
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Biosynthetic Strategies for Chemodiversity Generation in Marine Filamentous Cyanobacteria.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Biosynthetic Strategies for Chemodiversity Generation in Marine Filamentous Cyanobacteria./
作者:
Moss, Nathan Aaron.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:
203 p.
附註:
Source: Dissertations Abstracts International, Volume: 80-10, Section: B.
Contained By:
Dissertations Abstracts International80-10B.
標題:
Biological oceanography. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13805917
ISBN:
9781392020715
Biosynthetic Strategies for Chemodiversity Generation in Marine Filamentous Cyanobacteria.
Moss, Nathan Aaron.
Biosynthetic Strategies for Chemodiversity Generation in Marine Filamentous Cyanobacteria.
- Ann Arbor : ProQuest Dissertations & Theses, 2019 - 203 p.
Source: Dissertations Abstracts International, Volume: 80-10, Section: B.
Thesis (Ph.D.)--University of California, San Diego, 2019.
This item is not available from ProQuest Dissertations & Theses.
Organisms throughout the natural world have evolved different methods for biosynthesis of natural products, utilized in their native environs for defense, structure and signaling. One such method is the employment of modular polyketide synthase and non-ribosomal peptide synthetase enzymes to produce molecules from acetate and amino acid building blocks. The combinatorial capacity of these modules, combined with associated tailoring enzymes and unique protein-protein interaction strategies, has enabled a wide diversity of chemical structures and scaffolds. Many secondary metabolites or semi-synthetic derivatives have strong affinity for enzymatic targets and are used therapeutically to treat certain diseases. Photosynthetic marine filamentous cyanobacteria are prominent sources of bioactive natural products and present unique enzymatic methods for generating new chemical structures. This thesis describes the use of chemical biology techniques, including biochemistry, genomics, stable-isotope labeled feeding studies, NMR and mass spectrometry-based isolation and structure elucidation to explore and understand these novel methods for generating chemical structure diversity in cyanobacteria. Following an introduction and background in chapter one, chapter two describes new strategies for biosynthesis in the production of type A malyngamides in the species Okeania hirsuta sp. PAB10Feb10-1 and sp. PAP21Jun06-1, including neofunctionalization of a lipoic acid synthesis enzyme and ketoreductase domain inactivation. Chapter three of this thesis describes an unprecedented combinatorial approach to natural products biosynthesis in Moorea producens sp. ASI16Jul14-2: identical protein-protein interaction motifs guide a polyketide synthase-generated fatty acid tail to disparate downstream NRPS modules in the same biosynthetic gene cluster, representing a new mechanism for generating combinatorial chemical diversity in the productions of vatiamides A-F. Chapter four of this thesis highlights investigations toward understanding the biosynthesis of the t-butyl group in apratoxin A, a cyclic lipopeptide derived from cyanobacterium Moorea bouillonii PNG5-198. Lastly, chapter five presents a comprehensive overview of the findings described here, and discusses future avenues for research in microbial biosynthesis and natural products drug discovery as a whole.
ISBN: 9781392020715Subjects--Topical Terms:
2122748
Biological oceanography.
Subjects--Index Terms:
Biosynthesis
Biosynthetic Strategies for Chemodiversity Generation in Marine Filamentous Cyanobacteria.
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Organisms throughout the natural world have evolved different methods for biosynthesis of natural products, utilized in their native environs for defense, structure and signaling. One such method is the employment of modular polyketide synthase and non-ribosomal peptide synthetase enzymes to produce molecules from acetate and amino acid building blocks. The combinatorial capacity of these modules, combined with associated tailoring enzymes and unique protein-protein interaction strategies, has enabled a wide diversity of chemical structures and scaffolds. Many secondary metabolites or semi-synthetic derivatives have strong affinity for enzymatic targets and are used therapeutically to treat certain diseases. Photosynthetic marine filamentous cyanobacteria are prominent sources of bioactive natural products and present unique enzymatic methods for generating new chemical structures. This thesis describes the use of chemical biology techniques, including biochemistry, genomics, stable-isotope labeled feeding studies, NMR and mass spectrometry-based isolation and structure elucidation to explore and understand these novel methods for generating chemical structure diversity in cyanobacteria. Following an introduction and background in chapter one, chapter two describes new strategies for biosynthesis in the production of type A malyngamides in the species Okeania hirsuta sp. PAB10Feb10-1 and sp. PAP21Jun06-1, including neofunctionalization of a lipoic acid synthesis enzyme and ketoreductase domain inactivation. Chapter three of this thesis describes an unprecedented combinatorial approach to natural products biosynthesis in Moorea producens sp. ASI16Jul14-2: identical protein-protein interaction motifs guide a polyketide synthase-generated fatty acid tail to disparate downstream NRPS modules in the same biosynthetic gene cluster, representing a new mechanism for generating combinatorial chemical diversity in the productions of vatiamides A-F. Chapter four of this thesis highlights investigations toward understanding the biosynthesis of the t-butyl group in apratoxin A, a cyclic lipopeptide derived from cyanobacterium Moorea bouillonii PNG5-198. Lastly, chapter five presents a comprehensive overview of the findings described here, and discusses future avenues for research in microbial biosynthesis and natural products drug discovery as a whole.
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