國立高雄大學圖資館 |

語系: 繁體中文

說明(常見問題)

圖資館首頁

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

On the Biosynthesis of Triacsins.

Twigg, Frederick F.

On the Biosynthesis of Triacsins.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	On the Biosynthesis of Triacsins.
作者:	Twigg, Frederick F.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, 2020
面頁冊數:	91 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-04, Section: B.
附註:	Advisor: Zhang, Wenjun.
Contained By:	Dissertations Abstracts International82-04B.
標題:	Chemical engineering.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27994722
ISBN:	9798678170088

On the Biosynthesis of Triacsins.
Twigg, Frederick F.

On the Biosynthesis of Triacsins. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 91 p.

Source: Dissertations Abstracts International, Volume: 82-04, Section: B.

Thesis (Ph.D.)--University of California, Berkeley, 2020.

This item must not be sold to any third party vendors.

Natural products are a source of engineering innovation and design for small molecules due to their relevance to wide swaths of the chemical sector including medical, agricultural, food and fragrance, and commodity chemical fields. Their structural complexity comprising of numerous chiral centers and an abundance of heteroatoms makes organic synthesis challenging, expensive, and generally infeasible. While combinatorial chemistry hoped to address these obstacles by enabling rapid diversification and screening methods, it is still limited by access to an initial scaffold on which to act upon. As such there is great potential for leveraging biosynthesis in combination with synthetic strategies to facilitate sustainable production of new bioactive compounds. In this manuscript we present our findings on the biosynthesis of NN bonds in the context of the triacsin natural product family. By elucidating the biosynthesis of a compound with multiple NN chemical bonds, we have discovered multiple enzymatic strategies employed by nature to create a linkage which is synthetically challenging due to the inherent nucleophilicity of nitrogen atoms. As such this research provides insight into the biogenesis of NN bonds and addresses the aforesaid synthetic challenges in chemical access to new bioactive compounds.Triacsins are notable for the conserved N-hydroxytriazene moiety that all members of the family bear. In addition to two sequential NN bonds, the terminal nitrogen itself is a member of an additional heteroatom-heteroatom linkage in the form of a nitrogen-oxygen bond. As with many stories in natural product biosynthesis, this manuscript begins with the genomic sequencing of the originally reported native producer of triacsins. Mutagenesis and isotopically labeled precursor feeding led to the identification of the essential genes required for triacsin biosynthesis and led to the discovery of another native triacsin-producing organism. Cultivation of mutant strains and analysis of organic extracts from said strains led to the structural characterization of a key late-stage chemical intermediate that informed the biochemical timing of N-hydroxytriazene biosynthesis. Subsequent in vitro reconstitution of several encoded enzymes has advanced our knowledge of biochemical strategies for NN bond biogenesis. Finally, nascent work on the detailed characterization of an NN bond-forming enzyme will provide a full mechanistic understanding of this catalytic transformation. Collectively, this work contributes to the biocatalytic formation of NN bonds.

ISBN: 9798678170088Subjects--Topical Terms:

206267
Chemical engineering.
Subjects--Index Terms:

Biocatalysis

On the Biosynthesis of Triacsins.
LDR:03651nmm a2200361 4500 001 594573
005 20210521101657.5
008 210917s2020 ||||||||||||||||| ||eng d
020 $a 9798678170088
035 $a (MiAaPQ)AAI27994722
035 $a AAI27994722
040 $a MiAaPQ $c MiAaPQ
100 1 $a Twigg, Frederick F. $3 886589
245 1 0 $a On the Biosynthesis of Triacsins.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 91 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-04, Section: B.
500 $a Advisor: Zhang, Wenjun.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Natural products are a source of engineering innovation and design for small molecules due to their relevance to wide swaths of the chemical sector including medical, agricultural, food and fragrance, and commodity chemical fields. Their structural complexity comprising of numerous chiral centers and an abundance of heteroatoms makes organic synthesis challenging, expensive, and generally infeasible. While combinatorial chemistry hoped to address these obstacles by enabling rapid diversification and screening methods, it is still limited by access to an initial scaffold on which to act upon. As such there is great potential for leveraging biosynthesis in combination with synthetic strategies to facilitate sustainable production of new bioactive compounds. In this manuscript we present our findings on the biosynthesis of NN bonds in the context of the triacsin natural product family. By elucidating the biosynthesis of a compound with multiple NN chemical bonds, we have discovered multiple enzymatic strategies employed by nature to create a linkage which is synthetically challenging due to the inherent nucleophilicity of nitrogen atoms. As such this research provides insight into the biogenesis of NN bonds and addresses the aforesaid synthetic challenges in chemical access to new bioactive compounds.Triacsins are notable for the conserved N-hydroxytriazene moiety that all members of the family bear. In addition to two sequential NN bonds, the terminal nitrogen itself is a member of an additional heteroatom-heteroatom linkage in the form of a nitrogen-oxygen bond. As with many stories in natural product biosynthesis, this manuscript begins with the genomic sequencing of the originally reported native producer of triacsins. Mutagenesis and isotopically labeled precursor feeding led to the identification of the essential genes required for triacsin biosynthesis and led to the discovery of another native triacsin-producing organism. Cultivation of mutant strains and analysis of organic extracts from said strains led to the structural characterization of a key late-stage chemical intermediate that informed the biochemical timing of N-hydroxytriazene biosynthesis. Subsequent in vitro reconstitution of several encoded enzymes has advanced our knowledge of biochemical strategies for NN bond biogenesis. Finally, nascent work on the detailed characterization of an NN bond-forming enzyme will provide a full mechanistic understanding of this catalytic transformation. Collectively, this work contributes to the biocatalytic formation of NN bonds.
590 $a School code: 0028.
650 4 $a Chemical engineering. $3 206267
650 4 $a Biochemistry. $3 188609
650 4 $a Microbiology. $3 192943
653 $a Biocatalysis
653 $a Biosynthesis
653 $a Enzymology
653 $a N-N bonds
690 $a 0542
690 $a 0487
690 $a 0410
710 2 $a University of California, Berkeley. $b Chemical Engineering. $3 826984
773 0 $t Dissertations Abstracts International $g 82-04B.
790 $a 0028
791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27994722