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Polyketides, toxins and pigments in Penicillium marneffei

Emily W T Tam1, Chi-Ching Tsang2, Susanna K P Lau3,4,5,6

  • 1Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. emily.wt@gmail.com.

Toxins
|November 4, 2015
PubMed

Insights

Penicillium marneffei, a key fungal pathogen in Southeast Asia, has a large number of polyketide synthase genes. Four identified genes are crucial for producing pigments, including mycotoxins and virulence factors.

Area of Science:

  • Medical Mycology
  • Fungal Genomics
  • Secondary Metabolite Biosynthesis

Background:

  • Penicillium marneffei (Talaromyces marneffei) is a significant thermally dimorphic fungal pathogen in China and Southeast Asia.
  • Its incidence as an AIDS-defining illness has risen due to the HIV/AIDS pandemic.
  • Comparative genomic analysis reveals a unique genetic makeup in P. marneffei.

Purpose of the Study:

  • To investigate the polyketide synthase (PKS) gene repertoire in Penicillium marneffei.
  • To understand the phylogenetic distribution of PKS genes within P. marneffei.
  • To elucidate the role of specific PKS genes in fungal pigment biosynthesis and virulence.

Main Methods:

  • Genome sequencing of Penicillium marneffei.
  • Phylogenetic analysis of PKS genes.
  • Gene knockdown experiments.
  • Ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry (UHPLC-PDA/ESI-QTOF-MS) analysis.

Main Results:

  • Identification of 23 PKS genes and 2 PKS-NRPS hybrid genes in the P. marneffei genome, a higher number compared to Coccidioides immitis and Histoplasma capsulatum.
  • Phylogenetic analysis indicated even distribution of PKS genes, suggesting no recent lineage-specific expansion.
  • Experimental validation confirmed that at least four PKS genes are involved in the biosynthesis of various pigments, including mycotoxins like citrinin and virulence factors.

Conclusions:

  • The expanded PKS gene cluster in P. marneffei likely contributes to its pathogenicity.
  • Pigments synthesized by P. marneffei, potentially regulated by identified PKS genes, may act as mycotoxins and virulence factors.
  • Further research into these PKS genes could reveal novel therapeutic targets for P. marneffei infections.
Keywords:
Penicillium marneffeipigmentpolyketide synthase

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