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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
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Bifurcation drives the evolution of assembly-line biosynthesis
Thomas J Booth1,2, Kenan A J Bozhüyük1,3,4, Jonathon D Liston1
1Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK.
Nature Communications
|June 17, 2022
Summary
Nature evolves complex antibiotic assembly lines through gene duplication and neofunctionalization. This process creates new pathways, mirroring synthetic biology
Area of Science:
- Biochemistry
- Molecular Biology
- Evolutionary Biology
Background:
- Biosynthetic assembly-lines are crucial for producing antibiotic scaffolds.
- Rational reprogramming of these pathways has yielded limited success.
- Understanding Nature's assembly-line evolution offers insights into pathway design.
Purpose of the Study:
- To investigate evolutionary transitions in biosynthetic assembly-lines.
- To uncover mechanisms Nature uses to create and modify these pathways.
- To understand the evolution of antibiotic structures through pathway modification.
Main Methods:
- Examined the biosynthesis of anti-tubercular wollamides.
- Investigated gene duplication and neofunctionalization events.
- Analyzed intragenomic recombination as an initiation mechanism.
Main Results:
- Discovered pathway bifurcation driven by whole gene duplication and neofunctionalization.
- Demonstrated intragenomic recombination initiates neofunctionalization in wollamide biosynthesis.
- Showed pathway redundancy provides robustness for structural evolution.
Conclusions:
- Pathway bifurcation via gene duplication and neofunctionalization enables antibiotic structural evolution.
- Redundancy allows for significant structural changes, with gene loss or retention based on product advantage.
- This natural process parallels the design-build-test cycle in synthetic biology.
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