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Peer-reviewedCC BYGenome biology

The evolutionary processes of bacterial aromatic polyketide ketosynthases.

  1. 1Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China.
  2. 2Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China. [email protected].

Abstract

Background

The biosynthesis of bacterial aromatic polyketides (type II polyketides, T2PKs) employs a single set of catalysts (ketosynthases, KSs or KSα, with chain length factors, CLFs or KSβ) and iteratively assembles a carbon backbone with precise chain length control. Considering the increasing number of T2PKs discovered in laboratory settings, it is necessary to understand the evolutionary trajectories of KSs and CLFs.Results

We employ our recently developed algorithm, MAAPE, based on large protein language model to glean insights into the evolution process of KSs and CLFs. Our findings indicate the evolutionary history of KS and CLF domains from bacterial T2PKSs and identify a shared ancestral cluster (Cluster A), supporting a common origin. Despite structural homology, KSs and CLFs followed distinct evolutionary paths, shaped by coevolution and early horizontal gene transfer.Conclusions

Understanding the evolutionary lineage of these enzymes will illuminate the natural optimization processes of their functions and present opportunities for the rational design of novel polyketides with enhanced efficacy.

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BibTeX
@article{wang2026evolutionary,
  title = {{The evolutionary processes of bacterial aromatic polyketide ketosynthases.}},
  author = {Xiaoyu Wang and Qiandi Gao and Liangjun Ge and Zhiwei Qin},
  journal = {Genome biology},
  year = {2026},
  month = jul,
  doi = {10.1186/s13059-026-04215-7},
  url = {https://europepmc.org/article/MED/42907924},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The evolutionary processes of bacterial aromatic polyketide ketosynthases.
AU  - Xiaoyu Wang
AU  - Qiandi Gao
AU  - Liangjun Ge
AU  - Zhiwei Qin
PY  - 2026
DA  - 2026/07/01
JO  - Genome biology
DO  - 10.1186/s13059-026-04215-7
UR  - https://europepmc.org/article/MED/42907924
AB  - Background  The biosynthesis of bacterial aromatic polyketides (type II polyketides, T2PKs) employs a single set of catalysts (ketosynthases, KSs or KSα, with chain length factors, CLFs or KSβ) and iteratively assembles a carbon backbone with precise chain length control. Considering the increasing number of T2PKs discovered in laboratory settings, it is necessary to understand the evolutionary trajectories of KSs and CLFs.Results  We employ our recently developed algorithm, MAAPE, based on large protein language model to glean insights into the evolution process of KSs and CLFs. Our findings indicate the evolutionary history of KS and CLF domains from bacterial T2PKSs and identify a shared ancestral cluster (Cluster A), supporting a common origin. Despite structural homology, KSs and CLFs followed distinct evolutionary paths, shaped by coevolution and early horizontal gene transfer.Conclusions  Understanding the evolutionary lineage of these enzymes will illuminate the natural optimization processes of their functions and present opportunities for the rational design of novel polyketides with enhanced efficacy.
SN  - 1474-7596
SN  - 1474-760X
ER  -