Ketosynthase-associated C-terminal domains: extension control in modular polyketide synthases
🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 558 papers from lmmol's literature graph. Citations link to their source on PubMed.
| Protein | Papers |
|---|---|
| Fatty acid synthase | 31 |
| Fatty acid synthase | 16 |
| Fatty acid synthase | 14 |
| Reducing polyketide synthase hmp8 | 12 |
| Lovastatin nonaketide synthase, polyketide synthase component | 12 |
| Lovastatin nonaketide synthase, polyketide synthase component | 12 |
| Polyketide synthase Pks13 | 12 |
| Pikromycin polyketide synthase component PikAIV | 11 |
The KAsynt_C_assoc neighborhood is best understood as pathway-coupling machinery: C-terminal-associated domains stabilize productive chain transfer and shape where and how modules hand off chemistry.
1. Core architecture
The earliest architecture map for PKS systems already framed this as coordinated scaffolding where domain adjacency and docking logic define product geometry [1][2]. Structural work has extended this to show that C-terminal-associated regions and interface geometry determine whether extension follows the intended module route [3][4].
2. What changed
The modern literature increasingly distinguishes domain taxonomy from pathway state. In biosynthetic clusters, chain-growth control is linked to interactions between C-terminal modules and pathway timing rather than KR/KS naming alone [5][6][7][8].
3. Interpreting this topic in lmmol
Treat this topic as a control layer: prioritize papers where co-citation links align with demonstrated extension bottlenecks, pathogenicity shifts, or bioactive lipid/product transitions [9][10][11]. This helps distinguish homologous-looking modules from functionally central extension nodes [4][12].
4. Practical reading strategy on lmmol
For a working map, focus first on hubs shared across characterized clusters, then move into disease-linked examples where output topology reflects C-terminal control logic [1][13][14].
- Fatty acid synthase
- Erythronolide synthase EryA3
- Polyketide synthase Pks13
- Pikromycin polyketide synthase component
- 6-methylsalicylic acid synthase
References
- Donadio S., Staver M.J., McAlpine J.B., Swanson S.J. et al. Modular organization of genes required for complex polyketide biosynthesis. Science 1991. PubMed 700×
- Cortes J., Haydock S.F., Roberts G.A., Bevitt D.J. et al. An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 1990. PubMed 506×
- Tang Y., Kim C.Y., Mathews I.I., Cane D.E. et al. The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase. Proc. Natl. Acad. Sci. U.S.A 2006. PubMed 234×
- Khosla C., Tang Y., Chen A.Y., Schnarr N.A. et al. Structure and mechanism of the 6-deoxyerythronolide B synthase. Annu. Rev. Biochem 2007. PubMed 214×
- Ma S.M., Li J.W., Choi J.W., Zhou H. et al. Complete reconstitution of a highly reducing iterative polyketide synthase. Science 2009. PubMed 268×
- Bevitt D.J., Cortes J., Haydock S.F., Leadlay P.F. 6-deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea. Cloning of the structural gene, sequence analysis and inferred domain structure of the multifunctional enzyme. Eur. J. Biochem 1992. PubMed 159×
- Proctor R.H., Desjardins A.E., Plattner R.D., Hohn T.M. A polyketide synthase gene required for biosynthesis of fumonisin mycotoxins in Gibberella fujikuroi mating population A. Fungal Genet. Biol 1999. PubMed 220×
- Graham J.E., Clark-Curtiss J.E. Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Proc. Natl. Acad. Sci. U.S.A 1999. PubMed 369×
- Astarie-Dequeker C., Le Guyader L., Malaga W., Seaphanh F.K. et al. Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage invasion by inducing changes in the organization of plasma membrane lipids. PLoS Pathog 2009. PubMed 172×
- Jayakumar A., Tai M.-H., Huang W.-Y., Al-Feel W. et al. Human fatty acid synthase: properties and molecular cloning. Proc. Natl. Acad. Sci. U.S.A 1995. PubMed 196×
- Beck J., Ripka S., Siegner A., Schiltz E. et al. The multifunctional 6-methylsalicylic acid synthase gene of Penicillium patulum. Its gene structure relative to that of other polyketide synthases. Eur. J. Biochem 1990. PubMed 218×
- Whicher J.R., Dutta S., Hansen D.A., Hale W.A. et al. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature 2014. PubMed 146×
- Broadhurst R.W., Nietlispach D., Wheatcroft M.P., Leadlay P.F. et al. The structure of docking domains in modular polyketide synthases. Chem. Biol 2003. PubMed 183×
- Hoepfner D., McNamara C.W., Lim C.S., Studer C. et al. Selective and specific inhibition of the plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin. Cell Host Microbe 2012. PubMed 187×