Evolution and Diversity of Assembly-Line Polyketide Synthases
Chemical Reviews
|December 17, 2019
Summary
Assembly-line polyketide synthases (PKSs) are complex natural products. This review challenges gene duplication as the primary driver of PKS evolution and explores their vast chemical diversity.
Area of Science:
- Biochemistry
- Molecular Biology
- Synthetic Biology
Background:
- Assembly-line polyketide synthases (PKSs) are intricate protein machineries responsible for producing clinically relevant compounds.
- Their current diversity stems from evolutionary processes, including the development of multimodular architectures.
Purpose of the Study:
- To review PKS evolution, proposing an alternative model to the gene duplication hypothesis for multimodularity.
- To assess the potential diversity of PKS clusters and their products using bioinformatic analysis.
- To examine current methods for accessing PKS diversity and explore engineering strategies for expansion.
Main Methods:
- Review of existing literature on PKS evolution.
- Bioinformatic analysis of sequenced orphan PKS clusters.
- Examination of techniques for PKS discovery and engineering.
Main Results:
- A proposed model challenging the dominant role of gene duplication in the emergence of PKS multimodularity.
- An evaluation suggesting significant untapped diversity within assembly-line PKS clusters and their chemical products.
- An overview of established and emerging methods for PKS exploration and modification.
Conclusions:
- The evolution of PKS multimodularity may involve mechanisms beyond simple gene duplication.
- A vast chemical space remains unexplored within the PKS domain.
- Engineering PKS systems offers promising avenues for novel compound discovery.
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