Deletion and gene expression analyses define the paxilline biosynthetic gene cluster in Penicillium paxilli.
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.
Institute of Fundamental Sciences, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand. d.b.scott@massey.ac.nz
Barry
B
Scott
Carolyn A
CA
Young
Sanjay
S
Saikia
Lisa K
LK
McMillan
Brendon J
BJ
Monahan
Albert
A
Koulman
Jonathan
J
Astin
Carla J
CJ
Eaton
Andrea
A
Bryant
Ruth E
RE
Wrenn
Sarah C
SC
Finch
Brian A
BA
Tapper
Emily J
EJ
Parker
Geoffrey B
GB
Jameson
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D004224:Diterpenes / Q000378:metabolism; D004926:Escherichia coli; D017353:Gene Deletion; D015870:Gene Expression; D005800:Genes, Fungal; D056426:Genetic Loci; D026121:Indole Alkaloids / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009183:Mycotoxins / Q000378:metabolism; D010407:Penicillium / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004224:Diterpenes; D026121:Indole Alkaloids; D007211:Indoles; D009183:Mycotoxins; D014157:Transcription Factors; C048220:paxilline; C033673:lolitrem B