자료유형  

 학위논문

Control Number  

0016933141

International Standard Book Number  

9798379682231

Dewey Decimal Classification Number  

660

Main Entry-Personal Name  

Misa, Joshua Russell.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, Los Angeles., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(119 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Tang, Yi.

Dissertation Note  

Thesis (Ph.D.)--University of California, Los Angeles, 2023.

Restrictions on Access Note  

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

Summary, Etc.  

요약In addition to satisfying nutritional needs, humans have been consuming plants for medicinal and recreational purposes for millennia. The medicinal and recreational properties of plants are attributed to compounds that are not a product of the plant's core metabolism, but are rather secondary metabolites, also known as natural products. Monoterpene indole alkaloids (MIAs) are an expansive class of bioactive plant natural products, many of which have been named on the World Health Organization's List of Essential Medicines. Among MIAs' divergent structural complexity are psychoactive MIAs such as ibogaine and mitragynine which also hold therapeutic potential. However, low production from native plant hosts necessitates a more reliable source of these compounds to meet global demands in medicine and research. The recent explosion of synthetic biology toolsets and genomics data has enabled reconstitution of plant biosynthetic pathways to build complex MIA structures in alternative hosts.In this dissertation, we report on the development of a yeast-based platform for high-titer production of the universal MIA precursor, strictosidine. Our fed-batch platform produces ∼50 mg/L strictosidine, starting from the commodity chemicals geraniol and tryptamine, and is the highest titer reported to date. Next, we describe approaches to further optimize this platform and leverage it to produce strictosidine analogs. Bioprospecting homologs of pathway genes reveal the variants from Catharanthus roseus have the highest activity in yeast. Finally, we utilized our strictosidine platform to access bioactive MIAs such as heteroyohimbine and corynantheidine type MIAs. We also demonstrate our ability to access novel analogs of these compounds with our platform, which potentially have improved or divergent bioactivity from their native forms.

Subject Added Entry-Topical Term  

Chemical engineering.

Subject Added Entry-Topical Term  

Plant sciences.

Subject Added Entry-Topical Term  

Biochemistry.

Index Term-Uncontrolled  

Metabolic engineering

Index Term-Uncontrolled  

Monoterpene indole alkaloids

Index Term-Uncontrolled  

Strain engineering

Index Term-Uncontrolled  

Strictosidine

Index Term-Uncontrolled  

Synthetic biology

Index Term-Uncontrolled  

Yeast

Added Entry-Corporate Name  

University of California, Los Angeles Chemical Engineering 0294

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:642227