ArticlePLoS neglected tropical diseases2012
First discovery of two polyketide synthase genes for mitorubrinic acid and mitorubrinol yellow pigment biosynthesis and implications in virulence of Penicillium marneffei.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Article
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- Unraveling the dynamic transcriptomic changes during the dimorphic transition ofFrontiers in microbiology · 2024Article
- Differential innate immune responses of human macrophages and bronchial epithelial cells againstmSphere · 2023Article
- An Overlooked and Underrated Endemic Mycosis-Talaromycosis and the Pathogenic Fungus Talaromyces marneffei.Clinical microbiology reviews · 2023Review
- Core Steps to the Azaphilone Family of Fungal Natural Products.Chembiochem : a European journal of chemical biology · 2021Review
- Article
- Hybridorubrins A-D: Azaphilone Heterodimers from Stromata of Hypoxylon fragiforme and Insights into the Biosynthetic Machinery for Azaphilone Diversification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Genome-Based Classification of Strain 16-SW-7, a Marine Bacterium Capable of Converting B Red Blood Cells, asFrontiers in microbiology · 2021Article
- Fungal Extracellular Vesicles in Pathophysiology.Sub-cellular biochemistry · 2021Article
- First case report ofMedical mycology case reports · 2019Article
- Sixty Years from Segretain's Description: What Have We Learned and Should Learn About the Basic Mycology of Talaromyces marneffei?Mycopathologia · 2019Article
- Calcineurin A Is Essential in the Regulation of Asexual Development, Stress Responses and Pathogenesis inFrontiers in microbiology · 2019Article
- Natural products from thioester reductase containing biosynthetic pathways.Natural product reports · 2018Review
- Article
- Clinical Mass Spectrometry in the Bioinformatics Era: A Hitchhiker's Guide.Computational and structural biotechnology journal · 2018Review
- Molecular Networking-Based Metabolome and Bioactivity Analyses of Marine-Adapted Fungi Co-cultivated With Phytopathogens.Frontiers in microbiology · 2018Article
- Taxonomy and evolution ofComputational and structural biotechnology journal · 2018Review
- Review
- Article
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7 authors.
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Abstract
backgroundThe genome of P. marneffei, the most important thermal dimorphic fungus causing respiratory, skin and systemic mycosis in China and Southeast Asia, possesses 23 polyketide synthase (PKS) genes and 2 polyketide synthase nonribosomal peptide synthase hybrid (PKS-NRPS) genes, which is of high diversity compared to other thermal dimorphic pathogenic fungi. We hypothesized that the yellow pigment in the mold form of P. marneffei could also be synthesized by one or more PKS genes. METHODOLOGY/PRINCIPAL
findingsAll 23 PKS and 2 PKS-NRPS genes of P. marneffei were systematically knocked down. A loss of the yellow pigment was observed in the mold form of the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants. Sequence analysis showed that PKS11 and PKS12 are fungal non-reducing PKSs. Ultra high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry (MS) and MS/MS analysis of the culture filtrates of wild type P. marneffei and the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants showed that the yellow pigment is composed of mitorubrinic acid and mitorubrinol. The survival of mice challenged with the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants was significantly better than those challenged with wild type P. marneffei (P<0.05). There was also statistically significant decrease in survival of pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants compared to wild type P. marneffei in both J774 and THP1 macrophages (P<0.05). CONCLUSIONS/SIGNIFICANCE: The yellow pigment of the mold form of P. marneffei is composed of mitorubrinol and mitorubrinic acid. This represents the first discovery of PKS genes responsible for mitorubrinol and mitorubrinic acid biosynthesis. pks12 and pks11 are probably responsible for sequential use in the biosynthesis of mitorubrinol and mitorubrinic acid. Mitorubrinol and mitorubrinic acid are virulence factors of P. marneffei by improving its intracellular survival in macrophages.
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