東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Sterol Side-Chain Methylation in Unc...

Brown, Malory Onessa.

FindBook

Google Book

Amazon

博客來

Sterol Side-Chain Methylation in Uncultured Bacteria.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Sterol Side-Chain Methylation in Uncultured Bacteria./
作者:	Brown, Malory Onessa.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
面頁冊數:	155 p.
附註:	Source: Dissertations Abstracts International, Volume: 85-06, Section: B.
Contained By:	Dissertations Abstracts International85-06B.
標題:	DNA methylation. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30726851
ISBN:	9798381021264

Sterol Side-Chain Methylation in Uncultured Bacteria.
Brown, Malory Onessa.

Sterol Side-Chain Methylation in Uncultured Bacteria. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 155 p.

Source: Dissertations Abstracts International, Volume: 85-06, Section: B.

Thesis (Ph.D.)--Stanford University, 2023.

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

Sterols are polycyclic triterpenoid lipids required by eukaryotes for many critical cellular functions. In addition, sterols are quite recalcitrant and are preserved as sterane molecular fossils, or biomarkers, in sedimentary rocks up to 1.6 billion years old. Given the persistence of these molecules in ancient rocks and their wide distribution amongst extant eukaryotes, geologists often interpret steranes broadly as biomarkers of past eukaryotic life, although diverse bacteria are also known to produce sterol lipids. Sterols with certain modifications to the side-chain, such as methylations at the C-24 position, can act as more specific biomarkers given their restriction to certain eukaryotic lineages and absence in cultured bacteria. One such side-chain methylated sterane biomarker, 24- isopropylcholestane (24-ipc), has historically been attributed to sea sponges of the Demospongiae class. 24-ipc first appears in the Cryogenian and may therefore represent the first evidence of animals on Earth. However, enzymes that produce sterols with the 24- isopropyl side-chain have not been identified in any extant organism. In this dissertation, I investigate the biochemical requirements for sterol side-chain propylation and explore the potentional for sterol side-chain methylation in yet-uncultured bacteria more broadly through a combination of laboratory experiments and bioinformatic analyses. In Chapter 1, I find that several bacterial sterol methyltransferases (SMTs) identified in metagenomes methylate the sterol side-chain in vitro and identify three bacterial SMTs that produce sterols with the 24-isopropyl side-chain of the 24-ipc biomarker. Several functional metagenomic SMTs occur in sterol biosynthesis gene clusters suggesting yet-uncultured bacteria have the genomic capacity to produce side-chain alkylated sterols de novo. In Chapter 2, I identify a necessary but not sufficient glycine residue conserved among propylating bacterial SMTs that occurs in the active site of SMT model structures. The presence of this glycine residue can therefore act as indicator of an SMT's ability to produce 24-isopropyl sterols. In Chapter 3,I find that bacterial SMTs are widely distributed in the environment but are particularly enriched in sponge metagenomes. Bacterial SMTs are actively transcribed in wastewater, soil, creeks, hot springs, and estuaries. Together, the results presented in this dissertation suggest bacteria may be an overlooked source of side-chain methylated sterols in the rock record, provide a framework for predicting SMT function directly from sequencing data, and highlight environments that can be targeted for future cultivation of bacteria that produce side-chain methylated sterols. Overall, this work demonstrates how techniques in molecular biology, biochemistry, and bioinformatics can be leveraged to improve the interpretation of molecular fossils.

ISBN: 9798381021264Subjects--Topical Terms:

3560639
DNA methylation.

Sterol Side-Chain Methylation in Uncultured Bacteria.
LDR:04081nmm a2200385 4500 001 2395921
005 20240531084208.5
006 m o d
007 cr#unu||||||||
008 251215s2023 ||||||||||||||||| ||eng d
020 $a 9798381021264
035 $a (MiAaPQ)AAI30726851
035 $a (MiAaPQ)STANFORDcy756qp6377
035 $a AAI30726851
040 $a MiAaPQ $c MiAaPQ
100 1 $a Brown, Malory Onessa. $3 3765440
245 1 0 $a Sterol Side-Chain Methylation in Uncultured Bacteria.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 155 p.
500 $a Source: Dissertations Abstracts International, Volume: 85-06, Section: B.
500 $a Advisor: Francis, Christopher;Sperling, Erik;Welander, Paula.
502 $a Thesis (Ph.D.)--Stanford University, 2023.
506 $a This item must not be sold to any third party vendors.
520 $a Sterols are polycyclic triterpenoid lipids required by eukaryotes for many critical cellular functions. In addition, sterols are quite recalcitrant and are preserved as sterane molecular fossils, or biomarkers, in sedimentary rocks up to 1.6 billion years old. Given the persistence of these molecules in ancient rocks and their wide distribution amongst extant eukaryotes, geologists often interpret steranes broadly as biomarkers of past eukaryotic life, although diverse bacteria are also known to produce sterol lipids. Sterols with certain modifications to the side-chain, such as methylations at the C-24 position, can act as more specific biomarkers given their restriction to certain eukaryotic lineages and absence in cultured bacteria. One such side-chain methylated sterane biomarker, 24- isopropylcholestane (24-ipc), has historically been attributed to sea sponges of the Demospongiae class. 24-ipc first appears in the Cryogenian and may therefore represent the first evidence of animals on Earth. However, enzymes that produce sterols with the 24- isopropyl side-chain have not been identified in any extant organism. In this dissertation, I investigate the biochemical requirements for sterol side-chain propylation and explore the potentional for sterol side-chain methylation in yet-uncultured bacteria more broadly through a combination of laboratory experiments and bioinformatic analyses. In Chapter 1, I find that several bacterial sterol methyltransferases (SMTs) identified in metagenomes methylate the sterol side-chain in vitro and identify three bacterial SMTs that produce sterols with the 24-isopropyl side-chain of the 24-ipc biomarker. Several functional metagenomic SMTs occur in sterol biosynthesis gene clusters suggesting yet-uncultured bacteria have the genomic capacity to produce side-chain alkylated sterols de novo. In Chapter 2, I identify a necessary but not sufficient glycine residue conserved among propylating bacterial SMTs that occurs in the active site of SMT model structures. The presence of this glycine residue can therefore act as indicator of an SMT's ability to produce 24-isopropyl sterols. In Chapter 3,I find that bacterial SMTs are widely distributed in the environment but are particularly enriched in sponge metagenomes. Bacterial SMTs are actively transcribed in wastewater, soil, creeks, hot springs, and estuaries. Together, the results presented in this dissertation suggest bacteria may be an overlooked source of side-chain methylated sterols in the rock record, provide a framework for predicting SMT function directly from sequencing data, and highlight environments that can be targeted for future cultivation of bacteria that produce side-chain methylated sterols. Overall, this work demonstrates how techniques in molecular biology, biochemistry, and bioinformatics can be leveraged to improve the interpretation of molecular fossils.
590 $a School code: 0212.
650 4 $a DNA methylation. $3 3560639
650 4 $a Fungi. $3 571472
650 4 $a Bioinformatics. $3 553671
650 4 $a Eukaryotes. $3 3695352
650 4 $a Biosynthesis. $3 516407
650 4 $a Bacteria. $3 550366
650 4 $a Labeling. $3 3560710
650 4 $a Cholesterol. $3 3382101
650 4 $a Amino acids. $3 558768
650 4 $a Sterols. $3 915849
650 4 $a Genomes. $3 592593
650 4 $a Drinking water. $3 605014
650 4 $a E coli. $3 3556834
650 4 $a Chromatography. $3 1073639
650 4 $a Lipids. $3 558980
650 4 $a Creeks & streams. $3 3685269
650 4 $a Algae. $3 546231
650 4 $a Cloning. $3 571606
650 4 $a Steroids. $3 697464
650 4 $a Biomarkers. $3 2205735
650 4 $a Enzymes. $3 520899
650 4 $a Aquatic sciences. $3 3174300
650 4 $a Biochemistry. $3 518028
650 4 $a Genetics. $3 530508
650 4 $a Microbiology. $3 536250
650 4 $a Water resources management. $3 794747
690 $a 0715
690 $a 0792
690 $a 0487
690 $a 0369
690 $a 0410
690 $a 0595
710 2 $a Stanford University. $3 754827
773 0 $t Dissertations Abstracts International $g 85-06B.
790 $a 0212
791 $a Ph.D.
792 $a 2023
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30726851