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Updated: Nov 24, 2025
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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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Targeted Genome Mining-From Compound Discovery to Biosynthetic Pathway Elucidation
Nils Gummerlich1, Yuriy Rebets1, Constanze Paulus1
1Department of Pharmaceutical Biotechnology, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
Microorganisms
|December 23, 2020
Summary
Researchers explored Actinobacteria
Area of Science:
- Microbiology
- Natural Product Chemistry
- Genomics
Background:
- Actinobacteria are a rich source of novel antibiotic compounds.
- Genome sequencing reveals a gap between Actinobacteria's biosynthetic potential and actual natural product yields.
- Rediscovery of known compounds hinders natural product drug discovery.
Purpose of the Study:
- To unlock the biosynthetic potential of Actinobacteria for novel natural product discovery.
- To overcome limitations in natural product identification through systematic heterologous expression.
- To investigate the order Pseudonocardiales for unique biosynthetic gene clusters.
Main Methods:
- In-silico pre-selection of unique biosynthetic gene clusters.
- Systematic heterologous expression of selected gene clusters in Streptomyces lividans and Streptomyces albus.
- Purification, structure elucidation, mutational analysis, and feeding experiments for pathway deduction.
Main Results:
- Two novel natural products, pentangumycin and SEK90, were identified.
- Pentangumycin is an unusual angucyclinone.
- SEK90 is a new type II polyketide synthase shunt product.
- Biosynthetic pathways for pentangumycin and SEK90 were elucidated.
Conclusions:
- Heterologous expression of selected biosynthetic gene clusters is effective for discovering novel natural products.
- This approach successfully identified two new compounds from Saccharothrix espanaensis.
- The study demonstrates a viable strategy to translate genomic potential into tangible drug leads.
