A Chemoenzymatic Approach to Accessing Novel Isoprenoid Scaffolds
获取新型类异戊二烯支架的化学酶方法
基本信息
- 批准号:10582364
- 负责人:
- 金额:$ 14.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-01 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:AcidsActive SitesAddressAlcoholsAwardCannabinoidsCellsCollaborationsCoupledCouplingDiphosphatesEngineeringEnvironmentEnzymesEscherichia coliFarnesolFundingGenerationsGeranyltranstransferaseGoalsHumanIn SituIn VitroIndustryIsopreneKineticsKnowledgeLibrariesMedicineMetabolicMetabolic PathwayMethionineMethodologyMethodsMethyltransferaseMinnesotaModernizationMonitorMutagenesisNatural ProductsNatureNorth CarolinaParentsPathway interactionsPhosphotransferasesProcessProductionReactionS-AdenosylmethionineSourceSqualeneSqualene SynthetaseStructureStructure-Activity RelationshipSystemTechnologyTherapeuticUniversitiesVariantWorkanaloganalytical methodbasecatalystchemical synthesiscombinatorialfarnesyl pyrophosphatehigh throughput screeningin vivoinorganic phosphateisopentenyl pyrophosphateisoprenoidmetabolic engineeringmethionine adenosyltransferasenon-Nativenovelprenylscaffoldsynthetic biology
项目摘要
Summary of the funded parent award (1R01GM138800-01A1). Isoprenoids represent a diverse class of
compounds with a broad range of applications in medicine and industry. Their extraction from natural sources is
both challenging and potentially harmful to the environment, while the enormous structural complexity of many
isoprenoids makes traditional chemical synthesis nontrivial. Modern metabolic engineering and synthetic biology
approaches have overcome some of these difficulties, but issues related to metabolic flux and the limited
availability of the universal isoprenoid precursors complicate their widespread implementation. The artificial
pathways developed thus far have been solely focused on synthesizing dimethylallyl and isopentenyl diphosphates
and require additional enzymes for the generation of polyprenyl-diphosphates (polyprenyl-PPs). Thus, the
primary objective of this proposal is to develop an efficient strategy for the synthesis of both natural and unnatural
(poly)prenyl-PPs for downstream applications. This will be achieved using two complementary methods: i)
employing undecaprenol kinases and isopentenyl phosphate kinases; and ii) employing hydroxyethylthiazole
kinase, isopentenyl phosphate kinases, and farnesyl diphosphate synthase. Additionally, the two methods will
work in conjunction with isoprenoid methylatransferases to incorporate additional diversity into the polyprenyl-
PPs. The proposed studies include: i) structural and functional assessment of selected enzymes, ii) catalyst
engineering, and iii) optimization of coupled in vitro and in vivo platforms for the generation of diversified
libraries of select natural products. We expect these studies to generate: i) rules and concepts to advance
knowledge on structure-activity relationships in selected classes of enzymes; ii) an optimized, enzyme-coupled
platform to generate diversified substrates and isoprenoids; and iii) novel isoprenoid analogs with potential
therapeutic applications. Thus, the proposed work will offer unprecedented access to uniquely bioactive
isoprenoid libraries not readily accessible via traditional methods, and it stands to deepen our fundamental
understanding of four enzyme classes while also developing them into useful biocatalysts.
资助父母奖总结(1R01GM138800-01A1)。类异戊二烯代表了不同种类的
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Shanteri Singh其他文献
Shanteri Singh的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Shanteri Singh', 18)}}的其他基金
A Chemoenzymatic Approach to Accessing Novel Isoprenoid Scaffolds
获取新型类异戊二烯支架的化学酶方法
- 批准号:
10364914 - 财政年份:2022
- 资助金额:
$ 14.06万 - 项目类别:
A Chemoenzymatic Approach to Accessing Novel Isoprenoid Scaffolds
获取新型类异戊二烯支架的化学酶方法
- 批准号:
10543814 - 财政年份:2022
- 资助金额:
$ 14.06万 - 项目类别:
Development of chemoenzymatic platform for facile synthesis of alkyl-pyrophosphate analogs
开发化学酶平台以方便合成烷基焦磷酸类似物
- 批准号:
10182076 - 财政年份:2020
- 资助金额:
$ 14.06万 - 项目类别:
相似海外基金
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334970 - 财政年份:2024
- 资助金额:
$ 14.06万 - 项目类别:
Standard Grant
NSF-BSF: Towards a Molecular Understanding of Dynamic Active Sites in Advanced Alkaline Water Oxidation Catalysts
NSF-BSF:高级碱性水氧化催化剂动态活性位点的分子理解
- 批准号:
2400195 - 财政年份:2024
- 资助金额:
$ 14.06万 - 项目类别:
Standard Grant
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334969 - 财政年份:2024
- 资助金额:
$ 14.06万 - 项目类别:
Standard Grant
Mechanochemical synthesis of nanocarbon and design of active sites for oxygen reducton/evolution reactions
纳米碳的机械化学合成和氧还原/演化反应活性位点的设计
- 批准号:
23K04919 - 财政年份:2023
- 资助金额:
$ 14.06万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Creation of porous inorganic frameworks with controlled structure of metal active sites by the building block method.
通过积木法创建具有金属活性位点受控结构的多孔无机框架。
- 批准号:
22KJ2957 - 财政年份:2023
- 资助金额:
$ 14.06万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Catalysis of Juxaposed Active Sites Created in Nanospaces and Their Applications
纳米空间中并置活性位点的催化及其应用
- 批准号:
23K04494 - 财政年份:2023
- 资助金额:
$ 14.06万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of carbon active sites by modifying the oxygen containing functional groups and structures of carbons for utilizing to various catalytic reactions.
通过修饰碳的含氧官能团和结构来产生碳活性位点,用于各种催化反应。
- 批准号:
23K13831 - 财政年份:2023
- 资助金额:
$ 14.06万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
CAREER: CAS: Understanding the Chemistry of Palladium and Silyl Compounds to Design Catalyst Active Sites
职业:CAS:了解钯和甲硅烷基化合物的化学性质以设计催化剂活性位点
- 批准号:
2238379 - 财政年份:2023
- 资助金额:
$ 14.06万 - 项目类别:
Continuing Grant
CAS: Collaborative Research: Tailoring the Distribution of Transient vs. Dynamic Active Sites in Solid-Acid Catalysts and Their Impacts on Chemical Conversions
CAS:合作研究:定制固体酸催化剂中瞬时活性位点与动态活性位点的分布及其对化学转化的影响
- 批准号:
2154399 - 财政年份:2022
- 资助金额:
$ 14.06万 - 项目类别:
Standard Grant
Engineering of Active Sites in Heterogeneous Catalysts for Sustainable Chemical and Fuel Production.
用于可持续化学和燃料生产的多相催化剂活性位点工程。
- 批准号:
RGPIN-2019-06633 - 财政年份:2022
- 资助金额:
$ 14.06万 - 项目类别:
Discovery Grants Program - Individual