RUI: BIOPOLYMER - BIObricks POLYketide Metabolic EngineeRing platform

RUI：BIOPOLYMER - BIObricks 聚酮代谢工程环平台

• 批准号: 2015951
• 负责人: Stephen Nybo
• 金额: $ 40.79万
• 依托单位: Ferris State University (Inc.)
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2015951&HistoricalAwards=false
• 关键词: RUI; BIOPOLYMER; BIObricks; POLYketide; Metabolic

Soil bacteria make compounds called anthracyclinones (ACs), some of which have powerful therapeutic activity. ACs have complicated structures that are produced by enzymes found in the bacteria. This project will “mix-and-match” these enzymes to make novel ACs expected to have antibiotic and anticancer activity. As a Research in Undergraduate Institutions (RUI) project, it will attract undergraduate students to careers in science and engineering by involving them in the completion of the research aims. The professor and students will communicate to the public through a podcast. The overall objective of the project is to characterize polyketide synthase (PKS) genetic parts. These parts will be brought together in a platform (BIOPOLYMER) to form productive in vivo biosynthetic pathways. BIOPOLYMER will facilitate rational combinatorial biosynthesis. The central hypothesis is that combinatorial biosynthesis of selected PKS and post-PKS enzymes will facilitate the production of rationally designed anthracyclinones. The hypothesis will be tested in two specific aims: (1) characterize and develop PKS BioBricks parts for metabolic engineering of tricyclic anthracyclinones via heterologous expression of these components in actinomycetes; (2) characterize and develop post-PKS BioBricks parts for metabolic engineering of tetracyclic and oxidatively modified anthracyclinones in actinomycetes. At the completion of these studies, PKS and post-PKS gene sets will be identified that compose “new-to-nature” biosynthetic pathways for synthesizing new pharmaceuticals or commodity chemicals. The strains and vectors that are developed in this project period will be shared with the broader natural products community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

土壤细菌制成的化合物称为蒽环苷（AC），其中一些具有强大的治疗活性。 AC具有复杂的结构，这些结构是由细菌中发现的酶产生的。该项目将“混合”这些酶使新型ACS预计具有抗生素和抗癌活性。作为本科机构（RUI）项目的研究，它将通过使他们参与研究目标来吸引本科生从事科学和工程学的职业。教授和学生将通过播客与公众沟通。该项目的总体目的是表征聚酮化合酶（PKS）遗传部分。这些部分将在平台（生物聚合物）中汇集在一起​​，以形成在体内生物合成途径的生产力。生物聚合物将促进合理组合生物合成。中心假设是，选定的PK和POST-PKS酶的组合生物合成将促进合理设计的蒽环类酮的产生。该假设将以两个具体的目的进行检验：（1）表征和开发PKS Biobricks零件，用于三环蒽环类细胞酮的代谢工程，这些成分在放线菌中的异源表达； （2）表征和开发后-PKS Biobricks零件，用于在放线菌中的四环代谢工程和氧化修饰的蒽环节。这些研究完成时，将确定PK和POST-PKS基因集组成“新的”生物合成途径，以合成新的药物或商品化学品。在本项目期间开发的菌株和向量将与更广泛的天然产品社区共享。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来评估被认为是宝贵的支持。

项目成果

Renewed interests in the discovery of bioactive actinomycete metabolites driven by emerging technologies.

• DOI: 10.1111/jam.15225
• 发表时间: 2022-01
• 期刊: Journal of applied microbiology
• 影响因子: 4
• 作者: Ossai J;Khatabi B;Nybo SE;Kharel MK
• 通讯作者: Kharel MK

A BioBricks Metabolic Engineering Platform for the Biosynthesis of Anthracyclinones in Streptomyces coelicolor.

• DOI: 10.1021/acssynbio.2c00498
• 发表时间: 2022-12-16
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Wang, Rongbin;Nguyen, Jennifer;Hecht, Jacob;Schwartz, Nora;Brown, Katelyn, V;Ponomareva, Larissa, V;Niemczura, Magdalena;van Dissel, Dino;van Wezel, Gilles P.;Thorson, Jon S.;Metsa-Ketela, Mikko;Shaaban, Khaled A.;Nybo, S. Eric
• 通讯作者: Nybo, S. Eric

A BioBricks toolbox for metabolic engineering of the tetracenomycin pathway.

• DOI: 10.1002/biot.202100371
• 发表时间: 2022-03
• 期刊: Biotechnology journal
• 影响因子: 4.7
• 作者: Nguyen JT;Riebschleger KK;Brown KV;Gorgijevska NM;Nybo SE
• 通讯作者: Nybo SE