Polyketides, Toxins and Pigments in Penicillium marneffei

Abstract

<i>Penicillium marneffei</i> (synonym: <i>Talaromyces marneffei</i>) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining condition. Recently, we published the genome sequence of <i>P. marneffei</i>. In the <i>P. marneffei</i> genome, 23 polyketide synthase genes and two polyketide synthase-non-ribosomal peptide synthase hybrid genes were identified. This number is much higher than those of <i>Coccidioides immitis</i> and <i>Histoplasma capsulatum</i>, important pathogenic thermally dimorphic fungi in the Western world. Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in <i>Aspergillus</i> species and other fungi, suggesting that polyketide synthases in <i>P. marneffei</i> did not diverge from lineage-specific gene duplication through a recent expansion. Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in <i>P. marneffei</i>, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus.