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Toxins 2013, 5(8), 1422-1446; doi:10.3390/toxins5081422
Article

Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

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1 Institute of Fundamental Sciences, Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand 2 The Samuel Roberts Noble Foundation, Ardmore, OK 73401, USA 3 AgResearch, Grasslands Research Centre, Private Bag 11 008, Palmerston North 4442, New Zealand 4 AgResearch, Ruakura Research Centre, East Street, Private Bag 3123, Hamilton 3214, New Zealand
* Author to whom correspondence should be addressed.
Received: 5 June 2013 / Revised: 22 July 2013 / Accepted: 2 August 2013 / Published: 14 August 2013
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Abstract

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.
Keywords: indole-diterpene; paxilline; prenylation indole-diterpene; paxilline; prenylation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Scott, B.; Young, C.A.; Saikia, S.; McMillan, L.K.; Monahan, B.J.; Koulman, A.; Astin, J.; Eaton, C.J.; Bryant, A.; Wrenn, R.E.; Finch, S.C.; Tapper, B.A.; Parker, E.J.; Jameson, G.B. Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli. Toxins 2013, 5, 1422-1446.

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