Acyltransferase-1 systems: chain-building handoff and pathway retuning
🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 1,019 papers from lmmol's literature graph. Citations link to their source on PubMed.
| Protein | Papers |
|---|---|
| Fatty acid synthase | 31 |
| Conidial pigment polyketide synthase alb1 | 25 |
| Fatty acid synthase | 16 |
| Fatty acid synthase | 14 |
| Non-reducing polyketide synthase terA | 14 |
| Non-reducing polyketide synthase PKS12 | 13 |
| Reducing polyketide synthase hmp8 | 12 |
| Lovastatin nonaketide synthase, polyketide synthase component | 12 |
Acyltransferase-1 proteins mediate the handoff between acyl donors and downstream chain-building modules, making them central in both fatty-acid and polyketide assembly logic [1][2][3]. The family is less a single reaction type than a network of transfer interfaces that control when and where activated carbon chains enter larger biosynthetic programs.
1. Structural and functional anchors
Historically, this family was stabilized as a cross-cutting domain class in iteratively extending pathways. Structural snapshots and mutational work reinforced that specificity is often distributed across distant residues and transient docking events, not just active-site chemistry [2][4][5]. Later domain-domain work highlighted how these transfer steps coordinate with carrier and condensation systems to determine scaffold diversity.
2. Why this is active now
Recent work increasingly interprets acyltransferase activity as a lever for pathway rewiring. In fungal and bacterial systems, homologous modules are being compared not for linear homology but for transferable gating behavior under stress, iron control, and cluster regulation [6][7][8]. This explains why many recent studies blend genetic, regulatory, and biochemical framing rather than reporting isolated kinetic measurements.
3. From biosynthesis to intervention
The applied literature is now treating this family as a practical pivot between chemistry and phenotype: modifying transfer preferences alters natural-product outcomes and can change virulence-linked metabolites [7][9][10]. As with adjacent carrier and KS systems, this family’s strongest evidence chain sits at the boundary between module logic and ecological function, where transfer selectivity drives whole-pathway identity. [3][8]
4. How to read the lmmol graph
For this family, prioritize studies that connect transfer modules to concrete pathway products and ecological readouts, not just domain-presence surveys [2][11][3]. Those edges carry the highest signal stability in the literature graph and scale better for comparative review workflows.
References
- Kuhajda F.P., Jenner K., Wood F.D., Hennigar R.A. et al. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc. Natl. Acad. Sci. U.S.A 1994. PubMed 594×
- 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×
- 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×
- 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×
- Fujii I., Watanabe A., Sankawa U., Ebizuka Y. Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans. Chem. Biol 2001. PubMed 163×
- Bok J.W., Chiang Y.M., Szewczyk E., Reyes-Dominguez Y. et al. Chromatin-level regulation of biosynthetic gene clusters. Nat. Chem. Biol 2009. PubMed 285×
- 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×
- 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×
- Boehnert H.U., Fudal I., Dioh W., Tharreau D. et al. A putative polyketide synthase/peptide synthetase from Magnaporthe grisea signals pathogen attack to resistant rice. Plant Cell 2004. PubMed 232×
- Chen X.-H., Vater J., Piel J., Franke P. et al. Structural and functional characterization of three polyketide synthase gene clusters in Bacillus amyloliquefaciens FZB 42. J. Bacteriol 2006. PubMed 265×
- 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×