ArticleThe Journal of biological chemistry2016
Protein-Protein Interactions, Not Substrate Recognition, Dominate the Turnover of Chimeric Assembly Line Polyketide Synthases.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- KRstereo: Predicting β-Hydroxy Stereochemistry in Polyketides Using Protein Language Models.Journal of chemical information and modeling · 2026Article
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- Engineered polyketide synthases enable a microbial chassis for recyclable plastics with tunable properties.Nature biotechnology · 2026Article
- Graph neural networks can predict ketosynthase substrate specificity.Scientific reports · 2026Article
- Investigation of Domain-Domain Interaction between Acyl Carrier Protein and Thioesterase in Modular Polyketide Synthases.JACS Au · 2026Article
- Skeletal editing via multi-step engineering of a modular polyketide synthase.Nature communications · 2026Article
- Engineering Polyketide Stereocenters with Ketoreductase Domain Exchanges.Journal of the American Chemical Society · 2025Article
- Ancestral sequence reconstruction as a tool for structural analysis of modular polyketide synthases.Nature communications · 2025Article
- Structural basis for intermodular communication in assembly-line polyketide biosynthesis.Nature chemical biology · 2025Article
- The malonyl/acetyl-transferase from murine fatty acid synthase is a promiscuous engineering tool for editing polyketide scaffolds.Communications chemistry · 2024Article
- Structure and Mechanisms of Assembly-Line Polyketide Synthases.Annual review of biochemistry · 2024Review
- Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.Nature communications · 2024Article
- Module-Based Polyketide Synthase Engineering forACS synthetic biology · 2023Review
- Biosynthesis-Guided Discovery and Engineering of α-Pyrone Natural Products from Type I Polyketide Synthases.ACS chemical biology · 2023Article
- Enzymology of assembly line synthesis by modular polyketide synthases.Nature chemical biology · 2023Review
- Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.Nature structural & molecular biology · 2023Article
- Enzymology of standalone elongating ketosynthases.Chemical science · 2022Review
- Engineering the stambomycin modular polyketide synthase yields 37-membered mini-stambomycins.Nature communications · 2022Article
- Engineered biosynthesis of alkyne-tagged polyketides.Methods in enzymology · 2022Article
- Visualizing transiently associated catalytic domains in assembly-line biosynthesis using cryo-electron microscopy.Journal of structural biology · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The potential for recombining intact polyketide synthase (PKS) modules has been extensively explored. Both enzyme-substrate and protein-protein interactions influence chimeric PKS activity, but their relative contributions are unclear. We now address this issue by studying a library of 11 bimodular and 8 trimodular chimeric PKSs harboring modules from the erythromycin, rifamycin, and rapamycin synthases. Although many chimeras yielded detectable products, nearly all had specific activities below 10% of the reference natural PKSs. Analysis of selected bimodular chimeras, each with the same upstream module, revealed that turnover correlated with the efficiency of intermodular chain translocation. Mutation of the acyl carrier protein (ACP) domain of the upstream module in one chimera at a residue predicted to influence ketosynthase-ACP recognition led to improved turnover. In contrast, replacement of the ketoreductase domain of the upstream module by a paralog that produced the enantiomeric ACP-bound diketide caused no changes in processing rates for each of six heterologous downstream modules compared with those of the native diketide. Taken together, these results demonstrate that protein-protein interactions play a larger role than enzyme-substrate recognition in the evolution or design of catalytically efficient chimeric PKSs.
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