The evolutionary processes of bacterial aromatic polyketide ketosynthases.

Xiaoyu Wang, Qiandi Gao, Liangjun Ge, Zhiwei Qin

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Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 authors.

Xiaoyu Wang *Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China.

Qiandi Gao *Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China.

Liangjun GeCenter for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China.

Zhiwei QinCenter for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China. z.qin@bnu.edu.cn.ORCID https://orcid.org/0000-0002-1444-3684

Funding

Guangdong S&T Program 2024B1111130001Guangdong Talent Scheme 2021QN020100National Natural Science Foundation of China 32170079Natural Science Foundation of Guangdong Province 2024A1515012593

6 · The paper itself

Abstract

backgroundThe biosynthesis of bacterial aromatic polyketides (type II polyketides, T2PKs) employs a single set of catalysts (ketosynthases, KSs or KS

resultsWe 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.

conclusionsUnderstanding 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.

Indexed as

BacteriaBacterial ProteinsEvolution, MolecularPolyketidesPolyketide SynthasesAlgorithmsGene Transfer, HorizontalMultigene FamilyPhylogenyProtein DomainsBacterial ProteinsPolyketidesPolyketide SynthasesEvolutionary dynamicsLarge language modelNatural productPolyketide synthase

Identifiers

PMID42907924

DOI10.1186/s13059-026-04215-7

PMCPMC13685256

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