Polyketide synthase dehydrogenase (PS-DH): branch-point chemistry and pathway choice
🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 617 papers from lmmol's literature graph. Citations link to their source on PubMed.
| Protein | Papers |
|---|---|
| 6-hydroxymellein synthase terB | 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 |
| Lovastatin nonaketide synthase, polyketide synthase component | 12 |
| Norsolorinic acid synthase stcA | 12 |
| Orsellinic acid synthase armB | 11 |
PF14765 (PS-DH) sits at a recurring branch point where polyketide pathways decide reduction state, ring topology, and final bioactivity. In pathway terms, these dehydrogenase steps are often the first “decision gates” that lock in scaffold outcomes [1][2][3].
1. From domain to phenotype
Across fungal and actinomycete systems, PS-DH function is not just a terminal tailoring step; it is co-optimized with transcriptional and cluster-level context [4][5]. As a result, homologous dehydrogenase modules can support very different end products depending on upstream ketide architecture and partner domains, a pattern now repeatedly seen in pathogenic and industrially productive clusters [6][7].
2. What is new in modern studies
Recent corpus activity around this family emphasizes targeted module swaps, domain pairing, and in vitro reconstitution as ways to explain and redirect metabolite profiles [8][8][9]. Even older but still central genetic studies remain relevant because they establish baseline enzyme–domain complementarity that modern engineering now reuses [3][10][11].
3. The literature-graph lesson
For review synthesis, the strongest anchors are papers that jointly report: a dehydrogenase mutation/replacement, the resulting product profile, and mechanistic context for module adjacency [1][8][12]. Papers lacking this triplet tend to overstate PS-DH’s role by appearance rather than mechanism [10][10].
4. Practical implication for users
In the lmmol graph, this family is best consumed as a bridge between KS/AT/ACP modules and downstream tailoring outcomes. High-confidence neighbors are those sharing co-study with pathway clusters where PS-DH and chain-shaping decisions are experimentally linked, not simply co-annotated by family label [13][14].
References
- 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×
- 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×
- 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×
- 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×
- 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×
- Gaffoor I., Brown D.W., Plattner R., Proctor R.H. et al. Functional analysis of the polyketide synthase genes in the filamentous fungus Gibberella zeae (anamorph Fusarium graminearum). Eukaryot. Cell 2005. PubMed 151×
- Crawford J.M., Korman T.P., Labonte J.W., Vagstad A.L. et al. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature 2009. PubMed 134×
- Nielsen M.L., Nielsen J.B., Rank C., Klejnstrup M.L. et al. A genome-wide polyketide synthase deletion library uncovers novel genetic links to polyketides and meroterpenoids in Aspergillus nidulans. FEMS Microbiol. Lett 2011. PubMed 93×
- 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×
- Hendrickson L., Davis C.R., Roach C., Nguyen D.K. et al. Lovastatin biosynthesis in Aspergillus terreus: characterization of blocked mutants, enzyme activities and a multifunctional polyketide synthase gene. Chem. Biol 1999. PubMed 133×
- Kwan D.H., Sun Y., Schulz F., Hong H. et al. Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases. Chem. Biol 2008. PubMed 102×
- Matsunaga I., Bhatt A., Young D.C., Cheng T.Y. et al. Mycobacterium tuberculosis pks12 produces a novel polyketide presented by CD1c to T cells. J. Exp. Med 2004. PubMed 144×
- Gaffoor I., Trail F. Characterization of two polyketide synthase genes involved in zearalenone biosynthesis in Gibberella zeae. Appl. Environ. Microbiol 2006. PubMed 143×