Ultrahigh Throughput Microscale Mass Spectrometry for Pharmaceutical Prenylation Enzyme Engineering
用于药物异戊二烯化酶工程的超高通量微型质谱分析
基本信息
- 批准号:10325565
- 负责人:
- 金额:$ 25.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-25 至 2022-09-24
- 项目状态:已结题
- 来源:
- 关键词:AbateAcidsAddressAnabolismBiological AssayBusinessesCannabinoidsCellsCharacteristicsChemicalsChemistryCollaborationsComputer AssistedContract ServicesCouplingCustomDNA sequencingDetectionDevelopmentDimethylallyltranstransferaseElementsEngineeringEnzymesEquipmentEvolutionFamilyGenerationsGoalsIndustrializationLeadLibrariesLiquid substanceMass Spectrum AnalysisMethodsMicrofluidicsModificationMolecularNanoarray Analytical DeviceNatural ProductsOpticsPerformancePharmaceutical PreparationsPharmacologic SubstancePhasePreparationProcessProductionProtocols documentationProviderReagentRecoveryResearchResolutionRoboticsSamplingScanningServicesSlideSourceSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStructureSystemTechniquesTechnologyTestingTimeVariantVertebral columnWorkanalytical methodbasecannabigerolic acidcatalystcostcost effectivenessdesigndirect applicationdrug discoverydrug modificationdrug productionimprovedinnovationinstrumentnovelphysical propertyprenylationproduct developmentprogramsquantumresearch and developmentscreeningsynthetic biologytool
项目摘要
Project Summary
Biocatalyst can be key tools in the synthesis of natural product-based pharmaceuticals and as powerful components
of the pharmaceutical chemist’s drug modification kit. For example, the aromatic prenyltransferase NphB has utility in
the synthesis of common prenylated compounds or derived backbones include cannabinoids, alpha acids, beta acids,
phenylpropanoids, naphterpins, and marinones. The same enzyme also has utility as a general tool for compound
functionalization. Our partner, BioMediCan has developed a whole cell biocatalysis platform based on this enzyme for
production of natural and nonnatural rare cannabinoids. However, for all the attractive qualities and uses of enzyme-
based or whole-cell biocatalysis, NphB as well as many other enzymes have not evolved with the characteristics
required for industrial or pharmaceutical goals. These limitations arise because of the limitations of conventional
analytical methods and the narrow detection capabilities of the current suite of ultrahigh-throughput microfluidic
techniques. To develop novel high efficient platform and to improve the NphB biocatalyst, Fluid Discovery will engineer
a microfluidic based biocatalysis sample preparation system with capacities of high throughput sample processing
and low cost and enable its seamless coupling with matrix-assisted laser desorption/ionization (MALDI) mass
spectrometry for high sensitivity and general applicability. This method, called μMALDI-TOF, will not only allow Fluid
Discovery and BioMediCan to take the first steps towards becoming a key provider of novel compounds and enzymatic
tools, but also provide a quantum leap in biocatalyst discovery and engineering through a highly scalable and universal
screening platform. Our Phase I goal is to establish and demonstrate the capacity of this platform on engineering
NphB in whole cell biocatalysis. In Phase II, we will continue our work via engineering NphB for improving and
expanding the current whole-cell biocatalyst platform and initiate contracted service to early access synthetic biology
companies. Ultimately, we plan to leverage the generality of our product for applications in the generation of
biocatalysts for either green chemistry drug production or as tools for the molecular diversification that underlies lead
compound modification and optimization.
项目摘要
生物催化剂可以作为天然产物药物合成的关键工具和强大的成分
药剂师的药物改良工具包例如,芳香族异戊烯基转移酶NphB在以下方面具有效用:
普通异戊二烯化化合物或衍生骨架的合成包括大麻素,α酸,β酸,
苯丙素类、萘啶类和marinones。同样的酶也可用作化合物合成的一般工具。
功能化我们的合作伙伴BioMediCan基于这种酶开发了一种全细胞生物催化平台,
天然和非天然稀有大麻素的生产。然而,对于酶的所有吸引人的品质和用途-
基于或全细胞生物催化,NphB以及许多其他酶没有进化出的特性
用于工业或制药目的。这些局限性的出现是因为常规的
分析方法和目前的超高通量微流体套件的窄检测能力
技术.为了开发新的高效平台并改进NphB生物催化剂,Fluid Discovery将设计
具有高通量样品处理能力的基于微流体的生物催化样品制备系统
并且使其能够与基质辅助激光解吸/电离(MALDI)质谱无缝耦合
高灵敏度和普遍适用性。这种称为μMALDI-TOF的方法不仅可以让流体
Discovery和BioMediCan迈出第一步,成为新型化合物和酶制剂的主要供应商
工具,而且还通过高度可扩展和通用的
筛选平台我们的第一阶段目标是建立和展示这个平台的工程能力
全细胞生物催化中的NphB。在第二阶段,我们将继续我们的工作,通过工程NphB的改善和
扩展现有的全细胞生物催化剂平台,并启动抢先体验合成生物学的签约服务
企业最终,我们计划利用我们产品的通用性,
用于绿色化学药物生产的生物催化剂或作为铅的分子多样化的工具
复合改性和优化。
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)
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Adam R. Abate其他文献
FIND-seq: high-throughput nucleic acid cytometry for rare single-cell transcriptomics
FIND-seq:用于罕见单细胞转录组学的高通量核酸细胞计数术
- DOI:
10.1038/s41596-024-01021-y - 发表时间:
2024-07-22 - 期刊:
- 影响因子:16.000
- 作者:
Seung Won Shin;Prakriti Mudvari;Shravan Thaploo;Michael A. Wheeler;Daniel C. Douek;Francisco J. Quintana;Eli A. Boritz;Adam R. Abate;Iain C. Clark - 通讯作者:
Iain C. Clark
Adam R. Abate的其他文献
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{{ truncateString('Adam R. Abate', 18)}}的其他基金
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- 批准号:
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HIV阿片类药物使用者中潜在储库的分类和测序
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