ReviewBiochemistry2014
Assembly line polyketide synthases: mechanistic insights and unsolved problems.
Review in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 126 citations in OpenAlex.
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- Exploring marine-derived compounds as potential anti-cancer agents: Mechanisms and therapeutic implications.Cancer pathogenesis and therapy · 2026Review
- A novel transformer-based platform for the prediction and design of biosynthetic gene clusters for (un)natural products.PLoS computational biology · 2026Article
- Establishing Selectivity Trends with Reactions of Thioesterases and Semi-Synthetic Polyketides.Journal of the American Chemical Society · 2025Article
- Bacteria Under Metal Stress-Molecular Mechanisms of Metal Tolerance.International journal of molecular sciences · 2025Review
- Strategic Acyl Carrier Protein Engineering Enables Functional Type II Polyketide Synthase Reconstitution In Vitro.ACS chemical biology · 2025Article
- Discovery of Cryptic Natural Products Using High-Throughput Elicitor Screening on Agar Media.Biochemistry · 2025Article
- Characterization of the Flavin-Dependent Monooxygenase Involved in the Biosynthesis of the Nocardiosis-Associated Polyketide†.Biochemistry · 2024Article
- Discovering type I cis-AT polyketides through computational mass spectrometry and genome mining with Seq2PKS.Nature communications · 2024Article
- Genomic mining and diversity of assembly line polyketide synthases.Open biology · 2023Article
- Investigating A Multi-Domain Polyketide Synthase inMarine drugs · 2023Article
- Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase.Biochemistry · 2023Article
- Regulation of Multidrug Efflux Pumps by TetR Family Transcriptional Repressor Negatively Affects Secondary Metabolism in Streptomyces coelicolor A3(2).Applied and environmental microbiology · 2023Article
- The Ketosynthase Domain Controls Chain Length in Mushroom Oligocyclic Polyketide Synthases.Chembiochem : a European journal of chemical biology · 2023Article
- Bacterial Siderophores: Classification, Biosynthesis, Perspectives of Use in Agriculture.Plants (Basel, Switzerland) · 2022Review
- Conformational Selection Governs Carrier Domain Positioning inBiochemistry · 2022Article
- Metabolic channeling: predictions, deductions, and evidence.Molecular cell · 2021Review
- Properties of a "Split-and-Stuttering" Module of an Assembly Line Polyketide Synthase.The Journal of organic chemistry · 2021Article
- Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan.Nature communications · 2021Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Two hallmarks of assembly line polyketide synthases have motivated an interest in these unusual multienzyme systems, their stereospecificity and their capacity for directional biosynthesis. In this review, we summarize the state of knowledge regarding the mechanistic origins of these two remarkable features, using the 6-deoxyerythronolide B synthase as a prototype. Of the 10 stereocenters in 6-deoxyerythronolide B, the stereochemistry of nine carbon atoms is directly set by ketoreductase domains, which catalyze epimerization and/or diastereospecific reduction reactions. The 10th stereocenter is established by the sequential action of three enzymatic domains. Thus, the problem has been reduced to a challenge in mainstream enzymology, where fundamental gaps remain in our understanding of the structural basis for this exquisite stereochemical control by relatively well-defined active sites. In contrast, testable mechanistic hypotheses for the phenomenon of vectorial biosynthesis are only just beginning to emerge. Starting from an elegant theoretical framework for understanding coupled vectorial processes in biology [Jencks, W. P. (1980) Adv. Enzymol. Relat. Areas Mol. Biol. 51, 75-106], we present a simple model that can explain assembly line polyketide biosynthesis as a coupled vectorial process. Our model, which highlights the important role of domain-domain interactions, not only is consistent with recent observations but also is amenable to further experimental verification and refinement. Ultimately, a definitive view of the coordinated motions within and between polyketide synthase modules will require a combination of structural, kinetic, spectroscopic, and computational tools and could be one of the most exciting frontiers in 21st Century enzymology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.