Journal
TOXINS
Volume 5, Issue 8, Pages 1422-1446Publisher
MDPI
DOI: 10.3390/toxins5081422
Keywords
indole-diterpene; paxilline; prenylation
Categories
Funding
- New Zealand Foundation for Research, Science and Technology (FRST) [MAU-X0127, C10X0203]
- MRC [MC_EX_G0800783] Funding Source: UKRI
- Medical Research Council [MC_EX_G0800783] Funding Source: researchfish
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The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse). This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.
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