Part:BBa_K2352018
PDC1(pyruvate decarboxylase I)
UFlorida 2017
The enzyme encoded by PDCI, pyruvate decarboxylase I, catalyses the decarboxylation of the 2-oxo acids in the Ehrlich pathway. The 2-oxo acids are converted into aldehydes.
KUAS_Korea 2021
Written by: HyunJu Lee, Edited by: Sungwook Lee
Tryptophol was used by UFlorida in 2017 as the anti fungal agent against Bd. They referenced a research on identification of chemicals proudced in supernatants of cocultures of microbes sampled from the skin of a salamander species(Plethodon cinereus)(1)
The extracted chemicals were tested for Bd inhibition and the most potent chemical was identified by LC-MS(High Resolution-Mass Spectrometer). The results indicate this chemical is tryptophol.
Other references also indicate the Bd inhibitory activity of tryptophol. A research co-cultured J.lividium(Bd inhibitory microbe found in some amphibians) with Bd and then separated and identified active compounds. The MIC for the two compounds Tryptophol, Violacein were determined to be 68.9uM, 1.8uM respectively(2).
Interestingly, some research indicate tryptophol as a quorum sensing compound used by fungi(3).
Supernatants from Bd cultures grown for 5 days repressed Bd growth and when tryptophol was treated at differenct concentrations, 10, 23, 50, 100, 250, and 500 uM, and significant growth inhibition occurred at 100 uM. An autostimulatory mechanism is suggested from the fact that cultures treated with higher tryptophol produce more tryptophol and that cultures with higher density of cells express higher levels of putative ARO8 gene.
When tryptophol concentrations measured from cultures of Bd and Bsal(related pathogen) the concentrations ranged 133-652nM(bd) 1139-1251nM(bsal) respectively. This is in the nanomolar range which is much lower than the reported MIC; 68.9uM(2).</br>
Tryptophol is synthesized from the amino acid tryptophan through the Ehrlich pathway: a three-step biochemical reaction comprising transamination, decarboxylation, and reduction.(4) In Saccharomyces cerevisiae, tryptophol is Aro80p’s transcription activator. Tryptophol activates the transcription factor Aro80p and, consequently, the expression of the ARO9 and ARO10 transaminase and decarboxylase genes, which results in a positive feedback loop.(5)
References
- 1) Loudon Andrew H. et. al, 'Interactions between amphibians' symbiotic bacteria cause the production of emergent anti-fungal metabolites', Frontiers in Microbiology vol.5, 2014, URL=https://www.frontiersin.org/article/10.3389/fmicb.2014.00441
- 2) Brucker RM, et. al, Amphibian chemical defense: antifungal metabolites of the microsymbiont Janthinobacterium lividum on the salamander Plethodon cinereus. J Chem Ecol. 2008 Nov;34(11):1422-9. doi: 10.1007/s10886-008-9555-7. Epub 2008 Oct 24. PMID: 18949519
- 3) Verbrugghe Elin, Adriaensen Connie, Martel An, Vanhaecke Lynn, Pasmans Frank, Growth Regulation in Amphibian Pathogenic Chytrid Fungi by the Quorum Sensing Metabolite Tryptophol, Frontiers in Microbiology, Vol.9, 2019, URL=https://www.frontiersin.org/article/10.3389/fmicb.2018.03277, DOI=10.3389/fmicb.2018.03277
- 4) Hazelwood, Lucie & Daran, Jean-Marc & Van Maris, Antonius & Pronk, Jack & Dickinson, J. (2008). The Ehrlich Pathway for Fusel Alcohol Production: a Century of Research on Saccharomyces cerevisiae Metabolism. Applied and environmental microbiology. 74. 2259-66. 10.1128/AEM.02625-07.
- 5) Chen H, Fink GR. Feedback control of morphogenesis in fungi by aromatic alcohols. Genes Dev. 2006;20(9):1150-1161. doi:10.1101/gad.1411806
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000INCOMPATIBLE WITH RFC[1000]Illegal BsaI.rc site found at 400
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