Divergence of Carboxylate-Bridged Diiron Enzymes for Natural Product Biosynthesis
天然产物生物合成中羧酸桥二铁酶的分歧
基本信息
- 批准号:10581314
- 负责人:
- 金额:$ 19.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-20 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAnabolismAntibioticsBiochemicalBiochemical ReactionCarbonChemistryCritical PathwaysDioxygenEnzymesFolic AcidGenerationsGeneticHalogensHistidineIronKineticsMolecularNatural ProductsPathogenicityPathway interactionsProteinsRoleSiteStructureWorkcarboxylatechemical reactioncofactormicrobialpathogenic bacteriapharmacophoreprogramsscaffoldtool
项目摘要
PROJECT SUMMARY
Dinuclear iron enzymes (DIs) utilize a carboxylate- and histidine-coordinated cofactor to
affect synthetically challenging biochemical reactions. The recognized roles for DIs have
recently expanded to include several important natural product biosynthetic pathways,
including the generation of folate in pathogenic bacteria, the modulation of antibiotic
potency via halogen installation, and the synthesis of essential secondary metabolites
through carbon-carbon bond scission. To understand the molecular basis for how a very
similar cofactor and structural core can perform such diverse functions, we propose to
study three newly discovered DIs that contain nearly identical coordination motifs and
overall structural scaffolds but orchestrate chemistry in ways that fundamentally differ
from both each other and from well-studied DIs that instead perform the oxygenation of
substrates. The proposed work will utilize an array of spectroscopic, kinetic, and genetic
tools to identify key sites of the protein, substrate, and cofactor that enable such disparate
activities. An elucidation of the structural basis for DI functional reprogramming will
provide a biochemical template for the synthesis of new pharmacophores and the
molecular basis for pathways that are critical for microbial proliferation and pathogenicity.
项目总结
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Self-sacrificial tyrosine cleavage by an Fe:Mn oxygenase for the biosynthesis of para-aminobenzoate in Chlamydia trachomatis.
- DOI:10.1073/pnas.2210908119
- 发表时间:2022-09-27
- 期刊:
- 影响因子:11.1
- 作者:
- 通讯作者:
Excision of a Protein-Derived Amine for p-Aminobenzoate Assembly by the Self-Sacrificial Heterobimetallic Protein CADD.
通过自我牺牲异双金属蛋白 CADD 切除用于对氨基苯甲酸酯组装的蛋白质衍生胺。
- DOI:10.1021/acs.biochem.3c00406
- 发表时间:2023
- 期刊:
- 影响因子:2.9
- 作者:Phan,HanN;Manley,OliviaM;Skirboll,SydneyS;Cha,Lide;Hilovsky,Dalton;Chang,Wei-Chen;Thompson,PeterM;Liu,Xiaojing;Makris,ThomasM
- 通讯作者:Makris,ThomasM
Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production.
- DOI:10.1073/pnas.2221483120
- 发表时间:2023-05-30
- 期刊:
- 影响因子:11.1
- 作者:Rade, Leticia L.;Generoso, Wesley C.;Das, Suman;Souza, Amanda S.;Silveira, Rodrigo L.;Avila, Mayara C.;Vieira, Plinio S.;Miyamoto, Renan Y.;Lima, Ana B. B.;Aricetti, Juliana A.;de Melo, Ricardo R.;Milan, Natalia;Persinoti, Gabriela F.;Bonomi, Antonio M. F. L. J.;Murakami, Mario T.;Makris, Thomas M.;Zanphorlin, Leticia M.
- 通讯作者:Zanphorlin, Leticia M.
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Thomas M Makris其他文献
Thomas M Makris的其他文献
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{{ truncateString('Thomas M Makris', 18)}}的其他基金
Divergence of Carboxylate-Bridged Diiron Enzymes for Natural Product Biosynthesis
天然产物生物合成中羧酸桥二铁酶的分歧
- 批准号:
10304210 - 财政年份:2019
- 资助金额:
$ 19.26万 - 项目类别:
Divergence of Carboxylate-Bridged Diiron Enzymes for Natural Product Biosynthesis
天然产物生物合成中羧酸桥二铁酶的分歧
- 批准号:
10283095 - 财政年份:2019
- 资助金额:
$ 19.26万 - 项目类别:
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