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Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
Published on: March 12, 2020
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Recent developments in self-resistance gene directed natural product discovery
Yan Yan1, Nicholas Liu, Yi Tang
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA. yitang@ucla.edu.
Natural Product Reports
|January 9, 2020
Summary
Microbial natural products (NPs) can be toxic. Microbes use self-resistance enzymes (SREs) to protect themselves, and identifying SREs helps discover new bioactive NPs.
Area of Science:
- Biochemistry
- Microbiology
- Natural Products Chemistry
Background:
- Natural products (NPs) are vital sources for therapeutics and pesticides.
- Microbial producers of bioactive NPs often possess self-resistance mechanisms to prevent self-toxicity.
- Self-resistance enzymes (SREs), mutated versions of metabolic enzymes, confer resistance to toxic NPs while retaining function.
Purpose of the Study:
- To highlight natural product biosynthetic pathways that employ self-resistance genes for protection.
- To showcase how identifying SREs aids in natural product discovery and functional assignment.
- To bridge activity-guided and genome-driven approaches in natural product research.
Main Methods:
- Review and summarization of representative examples of NP biosynthetic pathways.
- Analysis of self-resistance gene identification strategies.
- Correlation of SRE presence with NP biological activity.
Main Results:
- Self-resistance genes are a common protective strategy in microbial NP biosynthesis.
- The presence of an SRE within a gene cluster can predict the biological activity of associated NPs.
- Recent discoveries have leveraged SRE identification for NP discovery.
Conclusions:
- Self-resistance genes are valuable indicators for identifying novel bioactive natural products.
- Identifying SREs facilitates the genome-driven discovery of natural products.
- This approach enhances the understanding of NP biosynthetic pathways and their functions.
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