Discovery and Characterization of Natural Product Systems

天然产物系统的发现和表征

基本信息

  • 批准号:
    10618882
  • 负责人:
  • 金额:
    $ 38.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-06-01 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary. In this competing renewal of R35 GM118101, we propose to focus on investigating and developing biocatalytic systems that generate complex natural products with high potential as therapeutic agents. This program has been highly productive with 34 publications over the past four years. Major progress continues toward studies on the function and structure of modular polyketide synthases (PKSs) from bacteria. A second thematic area involves studies on diverse bacterial and fungal indole alkaloid pathways for which we have reported important achievements on characterizing biosynthetic enzymes that catalyze pericyclic (e. g. Cope, Diels-Alder) reactions. We plan to build on these studies and also expand work on allied tailoring reactions for indole alkaloid structural diversification. Our work in the type I PKS area will focus on function and structure of key catalytic domains that we have identified to be gatekeepers in the catalytic cycle. By employing natural and unnatural advanced polyketide chain elongation intermediates with late stage PKS modules, we plan to develop methods to expand the biocatalytic potential of these remarkable molecular machines for assembly of macrolactone structures. Further glycosylation and late-stage hydroxylation/epoxidation methods will be employed to generate next generation macrolides for testing against a range of antibiotic-resistant human pathogens. Our work in the microbial indole alkaloids will focus on natural products whose core ring systems are derived from biocatalytic pericyclic reactions. Mechanistic understanding of these unusual processes is rapidly emerging, and their apparent flexibility indicates high potential for metabolite structural diversification. These efforts will be augmented by exploring late-stage tailoring enzymes capable of further modifying core indole alkaloid structures to generate a range of biologically active products with significant pharmaceutical potential.
项目总结。在R35 GM118101的竞争更新中,我们建议重点研究和研究

项目成果

期刊论文数量(23)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Engineering P450 TamI as an Iterative Biocatalyst for Selective Late-Stage C-H Functionalization and Epoxidation of Tirandamycin Antibiotics.
  • DOI:
    10.1021/acscatal.1c01460
  • 发表时间:
    2021-07-02
  • 期刊:
  • 影响因子:
    12.9
  • 作者:
    Espinoza RV;Haatveit KC;Grossman SW;Tan JY;McGlade CA;Khatri Y;Newmister SA;Schmidt JJ;Garcia-Borràs M;Montgomery J;Houk KN;Sherman DH
  • 通讯作者:
    Sherman DH
Chemoenzymatic synthesis of fluorinated polyketides.
  • DOI:
    10.1038/s41557-022-00996-z
  • 发表时间:
    2022-09
  • 期刊:
  • 影响因子:
    21.8
  • 作者:
  • 通讯作者:
Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412.
Identification of an unexpected shunt pathway product provides new insights into tirandamycin biosynthesis.
意外分流途径产物的鉴定为替兰霉素生物合成提供了新的见解
  • DOI:
    10.1016/j.tetlet.2016.11.080
  • 发表时间:
    2016-12-28
  • 期刊:
  • 影响因子:
    1.8
  • 作者:
    Zhang X;Li Z;Du L;Chlipala GE;Lopez PC;Zhang W;Sherman DH;Li S
  • 通讯作者:
    Li S
Ribosome-binding and anti-microbial studies of the mycinamicins, 16-membered macrolide antibiotics from Micromonospora griseorubida.
  • DOI:
    10.1093/nar/gkab684
  • 发表时间:
    2021-09-20
  • 期刊:
  • 影响因子:
    14.9
  • 作者:
    Breiner-Goldstein E;Eyal Z;Matzov D;Halfon Y;Cimicata G;Baum M;Rokney A;Ezernitchi AV;Lowell AN;Schmidt JJ;Rozenberg H;Zimmerman E;Bashan A;Valinsky L;Anzai Y;Sherman DH;Yonath A
  • 通讯作者:
    Yonath A
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DAVID H SHERMAN其他文献

DAVID H SHERMAN的其他文献

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{{ truncateString('DAVID H SHERMAN', 18)}}的其他基金

Discovery and Characterization of Natural Product Systems
天然产物系统的发现和表征
  • 批准号:
    10418743
  • 财政年份:
    2016
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery and Characterization of Natural Product Systems-Research Supplement to Promote Diversity
天然产物系统的发现和表征-促进多样性的研究补充
  • 批准号:
    9905666
  • 财政年份:
    2016
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery and Characterization of Natural Product Systems
天然产物系统的发现和表征
  • 批准号:
    10206351
  • 财政年份:
    2016
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery and Characterization of Natural Product Systems
天然产物系统的发现和表征
  • 批准号:
    9277486
  • 财政年份:
    2016
  • 资助金额:
    $ 38.11万
  • 项目类别:
LIPOPOLYSACCHARIDE TRANSPORT
脂多糖运输
  • 批准号:
    8363366
  • 财政年份:
    2011
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery of Natural Product based Drugs and Bioenergetic Materials from CR
从 CR 中发现基于天然产物的药物和生物能材料
  • 批准号:
    8488515
  • 财政年份:
    2009
  • 资助金额:
    $ 38.11万
  • 项目类别:
of Natural Product based Drugs and Bioenergetic Materials from Costa Rican Biota
来自哥斯达黎加生物群的基于天然产物的药物和生物能材料
  • 批准号:
    7741888
  • 财政年份:
    2009
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery of Natural Product based Drugs and Bioenergetic Materials from CR
从 CR 中发现基于天然产物的药物和生物能材料
  • 批准号:
    8287155
  • 财政年份:
    2009
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery of Natural Product based Drugs and Bioenergetic Materials from CR
从 CR 中发现基于天然产物的药物和生物能材料
  • 批准号:
    8112694
  • 财政年份:
    2009
  • 资助金额:
    $ 38.11万
  • 项目类别:
Discovery of Natural Product based Drugs and Bioenergetic Materials from CR
从 CR 中发现基于天然产物的药物和生物能材料
  • 批准号:
    7935324
  • 财政年份:
    2009
  • 资助金额:
    $ 38.11万
  • 项目类别:

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玛丽·杜瓦尔 (Marie Duval) 介绍艾丽·斯洛珀 (Ally Sloper):1869-85 年伦敦的女漫画家和受欢迎的剧院。
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