Data-driven discovery of novel terpene synthases and its utilization for efficient production of structurally divergent compounds through a light control system in bacteria
| Project/Area Number |
23K13898
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38040:Bioorganic chemistry-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Vo NgocQuynhNhu 国立研究開発法人理化学研究所, 環境資源科学研究センター, 特別研究員 (60888543)
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2024: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Terpene synthases / Drimenol / Sesquiterpenes / Marine bacteria / Gene clusters / Blue-light switch / Metabolic engineering |
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| Outline of Research at the Start |
By genomic mining approaches, I will further discover unknown terpene synthase genes of marine bacterial origin and elucidate their clustered biosynthetic genes. In addition, I will apply a light switch system on Streptomyces to produce bioactive terpenoids efficiently by utilizing novel genes.
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| Outline of Annual Research Achievements |
The goal of this study is to understand the diversity and biosynthetic potential of terpenoids in bacteria, especially marine bacteria. To achieve this goal, during the FY2023, as originally planned, I have investigated and found a number of promising bacterial terpene synthase genes, using our optimized genomic data mining method. I have characterized several terpene synthase enzymes by in vitro enzymatic assays and gas chromatography-mass spectrometry, and discovered novel enzymatic activities.
Moreover, I have successfully found the biosynthetic genes clustered with drimenol synthases encoded in marine bacterial genomes for drimenol synthesis, which are uniquely conserved. I have also verified the drimenol production in marine bacteria and suggested the evolutionary features of the drimenol gene cluster in marine bacteria. We have summarized these findings in a scientific paper and we will submit it for publication.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
As stated in the "Summary of Research Achievements", I have investigated and found more unknown terpene synthase genes of bacterial origin by genomic data mining and biochemical validation. In addition, I have elucidated the existence of core biosynthetic genes involved in drimenol biosynthesis and their distribution across marine bacterial genomes, verifying the accumulation of drimenol, a highly active sesquiterpene, in bacteria (manuscript in preparation). With those achievements, the status to date of my research project is progressing smoothly, which is approaching to the goal of advancing our understanding of the diversity and biosynthetic origin of terpenoids derived from bacteria including marine bacteria.
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| Strategy for Future Research Activity |
As for future work, I will further perform functional analysis using in vitro enzymatic assays and gas chromatography-mass spectrometry of promising candidate terpene synthases harvested from data mining approach to identify more novel enzymes with unique structures and reaction mechanisms that can make novel active terpenoids. In addition, I will elucidate biosynthetic genes, with a focus on prenyltransferases and monooxygenases, clustered with those characterized terpene synthases to make structurally divergent compounds. At the same time, I will construct and characterize the new bacterial blue-light switch platform to be ready for the introduction of novel bacterial terpene synthase genes and their clustered genes to enhance the production of target compounds.
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Report
(1 results)
Research Products
(2 results)
