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Biosynthesis and Function of Cardiac Glycosides in the Crucifer Genus Erysimum
Biosynthesis and Function of Cardiac Glycosides in the Crucifer Genus Erysimum
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151316
- ISBN
- 9798382841809
- DDC
- 580
- 서명/저자
- Biosynthesis and Function of Cardiac Glycosides in the Crucifer Genus Erysimum
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 196 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Includes supplementary digital materials.
- 주기사항
- Advisor: Jander, Georg.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 요약Erysimum is a diverse genus within the Brassicaceae consisting of several hundred species distributed across the temperate northern hemisphere. Like most members of the mustard family, Erysimum produces evolutionarily ancestral glucosinolates as a defense against herbivores. However, its recent and rapid radiation has been partially attributed to its 'escape from herbivory' via the evolution of a different group toxic compounds called cardiac glycosides or cardenolides. Cardiac glycosides have been used to treat heart conditions for hundreds of years and are on the World Health Organization's list of essential medicines. However, the biosynthetic pathway remains unknown. In Chapter 1 of this dissertation, I provide background information and describe the development of genetic resources for the study of cardiac glycoside biosynthesis in Erysimum cheiranthoides, including an improved genome assembly and a protocol for floral dip stable transformation. In subsequent chapters, I use metabolomic and transcriptomic datasets to identify candidate genes for cardiac glycoside biosynthesis and test candidate gene function using CRISPR/Cas9-mediated gene editing, in vitro assays with purified recombinant proteins, and pathway reassembly in heterologous systems. In total, I identified and characterized seven enzymes that are involved in cardiac glycoside biosynthesis in E. cheiranthoides. In Chapter 2, I describe EcCYP87A126, a cytochrome P450 that initiates cardiac glycoside biosynthesis via sterol side chain cleavage. Chapter 3 explores Ec3βHSD (a hydroxysteroid dehydrogenase), Ec3KSI (a ketosteroid isomerase), EcP5βR2 (a progesterone 5β-reductase), and EcDET2 (a steroid 5α-reductase), which are involved in oxidation and reduction of the steroid core and help to explain variation in cardiac glycoside structure that is observed across the Erysimum genus. Finally, I discuss two 2-oxoglutarate dependent dioxygenases that are required for cardiac glycoside biosynthesis in Chapter 4. Through the identification of these enzymes, I begin to untangle the evolutionary history of cardiac glycoside biosynthesis in the genus, and I use cardiac glycoside-deficient mutant lines to better understand their role in protection against insect herbivores in an already well-defended plant lineage. These results represent a step forward in our understanding of cardiac glycoside biosynthesis and function, with implications for engineering the pathway in heterologous systems.
- 일반주제명
- Plant sciences
- 일반주제명
- Biochemistry
- 일반주제명
- Molecular biology
- 일반주제명
- Evolution & development
- 일반주제명
- Genetics
- 키워드
- Cardenolides
- 키워드
- Erysimum
- 키워드
- Herbivory
- 기타저자
- Cornell University Plant Biology
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151316
■006m o d
■007cr#unu||||||||
■020 ▼a9798382841809
■035 ▼a(MiAaPQ)AAI31238499
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a580
■1001 ▼aYounkin, Gordon Curtis.▼0(orcid)0000-0002-3735-3534
■24510▼aBiosynthesis and Function of Cardiac Glycosides in the Crucifer Genus Erysimum
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a196 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aIncludes supplementary digital materials.
■500 ▼aAdvisor: Jander, Georg.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aErysimum is a diverse genus within the Brassicaceae consisting of several hundred species distributed across the temperate northern hemisphere. Like most members of the mustard family, Erysimum produces evolutionarily ancestral glucosinolates as a defense against herbivores. However, its recent and rapid radiation has been partially attributed to its 'escape from herbivory' via the evolution of a different group toxic compounds called cardiac glycosides or cardenolides. Cardiac glycosides have been used to treat heart conditions for hundreds of years and are on the World Health Organization's list of essential medicines. However, the biosynthetic pathway remains unknown. In Chapter 1 of this dissertation, I provide background information and describe the development of genetic resources for the study of cardiac glycoside biosynthesis in Erysimum cheiranthoides, including an improved genome assembly and a protocol for floral dip stable transformation. In subsequent chapters, I use metabolomic and transcriptomic datasets to identify candidate genes for cardiac glycoside biosynthesis and test candidate gene function using CRISPR/Cas9-mediated gene editing, in vitro assays with purified recombinant proteins, and pathway reassembly in heterologous systems. In total, I identified and characterized seven enzymes that are involved in cardiac glycoside biosynthesis in E. cheiranthoides. In Chapter 2, I describe EcCYP87A126, a cytochrome P450 that initiates cardiac glycoside biosynthesis via sterol side chain cleavage. Chapter 3 explores Ec3βHSD (a hydroxysteroid dehydrogenase), Ec3KSI (a ketosteroid isomerase), EcP5βR2 (a progesterone 5β-reductase), and EcDET2 (a steroid 5α-reductase), which are involved in oxidation and reduction of the steroid core and help to explain variation in cardiac glycoside structure that is observed across the Erysimum genus. Finally, I discuss two 2-oxoglutarate dependent dioxygenases that are required for cardiac glycoside biosynthesis in Chapter 4. Through the identification of these enzymes, I begin to untangle the evolutionary history of cardiac glycoside biosynthesis in the genus, and I use cardiac glycoside-deficient mutant lines to better understand their role in protection against insect herbivores in an already well-defended plant lineage. These results represent a step forward in our understanding of cardiac glycoside biosynthesis and function, with implications for engineering the pathway in heterologous systems.
■590 ▼aSchool code: 0058.
■650 4▼aPlant sciences
■650 4▼aBiochemistry
■650 4▼aMolecular biology
■650 4▼aEvolution & development
■650 4▼aGenetics
■653 ▼aCardenolides
■653 ▼aCardiac glycosides
■653 ▼aErysimum
■653 ▼aHerbivory
■690 ▼a0479
■690 ▼a0487
■690 ▼a0307
■690 ▼a0412
■690 ▼a0369
■71020▼aCornell University▼bPlant Biology.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161145▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
