First Discovery of Two Polyketide Synthase Genes for Mitorubrinic Acid and Mitorubrinol Yellow Pigment Biosynthesis and Implications in Virulence of Penicillium marneffei

ABSTRACT Penicillium marneffei is the most important thermal dimorphic, pathogenic fungus endemic in China and Southeast Asia and is particularly important in HIV-positive patients. We report the 28,887,485-bp draft genome sequence of P. marneffei , which contains its complete mitochondrial genome, sexual cycle genes, a high diversity of Mp1p homologues, and polyketide synthase genes.

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Two Novel Classes of Enzymes Are Required for the Biosynthesis of Aurofusarin in Fusarium graminearum

Journal of Biological Chemistry ◽

10.1074/jbc.m110.179853 ◽

2011 ◽

Vol 286 (12) ◽

pp. 10419-10428 ◽

Cited By ~ 56

Author(s):

Rasmus J. N. Frandsen ◽

Claes Schütt ◽

Birgitte W. Lund ◽

Dan Staerk ◽

John Nielsen ◽

...

Keyword(s):

Plasma Membrane ◽

Fusarium Graminearum ◽

Polyketide Synthase ◽

Functional Characterization ◽

Extracellular Enzyme ◽

Gene Replacement ◽

Orphan Genes ◽

Pigment Biosynthesis ◽

Targeted Gene Replacement

Previous studies have reported the functional characterization of 9 out of 11 genes found in the gene cluster responsible for biosynthesis of the polyketide pigment aurofusarin in Fusarium graminearum. Here we reanalyze the function of a putative aurofusarin pump (AurT) and the two remaining orphan genes, aurZ and aurS. Targeted gene replacement of aurZ resulted in the discovery that the compound YWA1, rather than nor-rubrofusarin, is the primary product of F. graminearum polyketide synthase 12 (FgPKS12). AurZ is the first representative of a novel class of dehydratases that act on hydroxylated γ-pyrones. Replacement of the aurS gene resulted in accumulation of rubrofusarin, an intermediate that also accumulates when the GIP1, aurF, or aurO genes in the aurofusarin cluster are deleted. Based on the shared phenotype and predicted subcellular localization, we propose that AurS is a member of an extracellular enzyme complex (GIP1-AurF-AurO-AurS) responsible for converting rubrofusarin into aurofusarin. This implies that rubrofusarin, rather than aurofusarin, is pumped across the plasma membrane. Replacement of the putative aurofusarin pump aurT increased the rubrofusarin-to- aurofusarin ratio, supporting that rubrofusarin is normally pumped across the plasma membrane. These results provide functional information on two novel classes of proteins and their contribution to polyketide pigment biosynthesis.

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Novel Polyketide Synthase from Nectria haematococca

Applied and Environmental Microbiology ◽

10.1128/aem.70.5.2984-2988.2004 ◽

2004 ◽

Vol 70 (5) ◽

pp. 2984-2988 ◽

Cited By ~ 48

Author(s):

Stephane Graziani ◽

Christelle Vasnier ◽

Marie-Josee Daboussi

Keyword(s):

Polyketide Synthase ◽

Fungal Growth ◽

Type I ◽

Biosynthetic Pathways ◽

Carrier Proteins ◽

Nectria Haematococca ◽

Acyl Carrier Proteins ◽

Asexual Sporulation ◽

Ketoacyl Synthase ◽

Pigment Biosynthesis

ABSTRACT We identified a polyketide synthase (PKS) gene, pksN, from a strain of Nectria haematococca by complementing a mutant unable to synthesize a red perithecial pigment. pksN encodes a 2,106-amino-acid polypeptide with conserved motifs characteristic of type I PKS enzymatic domains: β-ketoacyl synthase, acyltransferase, duplicated acyl carrier proteins, and thioesterase. The pksN product groups with the Aspergillus nidulans WA-type PKSs involved in conidial pigmentation and melanin, bikaverin, and aflatoxin biosynthetic pathways. Inactivation of pksN did not cause any visible change in fungal growth, asexual sporulation, or ascospore formation, suggesting that it is involved in a specific developmental function. We propose that pksN encodes a novel PKS required for the perithecial red pigment biosynthesis.

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