Unprecedented Immunosuppressive Polyketides from <i>Daldinia eschscholzii</i>, a Mantis‐Associated Fungus

Zhang, Ying Lao; Ge, Hui; Zhao, Wei; Dong, Hao; Xu, Qiang; Li, Shu Hua; Li, Jing; Zhang, Jie; Song, Yong; Tan, Ren Xiang

doi:10.1002/ange.200801284

Cited by 34 publications

(22 citation statements)

References 20 publications

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“…The biological activities of fungal polyketides span from potent carcinogenic toxins (aflatoxin) over immunosuppressants (dalesconols), anti-tumor compounds (aspergiolide A) to block-buster cholesterol-lowering drugs (statins) [1-3]. In addition, many fungal polyketides also display vibrant colors due to their polyaromatic structures, which have made them attractive for the textile and food industries as natural dyes [4,5].…”

Section: Introductionmentioning

confidence: 99%

Reconstruction of the biosynthetic pathway for the core fungal polyketide scaffold rubrofusarin in Saccharomyces cerevisiae

Rugbjerg

Næsby

Mortensen³

et al. 2013

Microb Cell Fact

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BackgroundFungal polyketides include commercially important pharmaceuticals and food additives, e.g. the cholesterol-lowering statins and the red and orange monascus pigments. Presently, production relies on isolation of the compounds from the natural producers, and systems for heterologous production in easily fermentable and genetically engineerable organisms, such as Saccharomyces cerevisiae and Escherichia coli are desirable. Rubrofusarin is an orange polyketide pigment that is a common intermediate in many different fungal biosynthetic pathways.ResultsIn this study, we established a biosynthetic pathway for rubrofusarin in S. cerevisiae. First, the Fusarium graminearum gene encoding polyketide synthase 12 (PKS12) was heterologously co-expressed with the Aspergillus fumigatus gene encoding phosphopantetheinyl transferase (npgA) resulting in production of YWA1. This aromatic heptaketide intermediate was converted into nor-rubrofusarin upon expression of the dehydratase gene aurZ from the aurofusarin gene cluster of F. graminearum. Final conversion into rubrofusarin was achieved by expression of the O-methyltransferase encoding gene aurJ, also obtained from the aurofusarin gene cluster, resulting in a titer of 1.1 mg/L. Reduced levels of rubrofusarin were detected when expressing PKS12, npgA, and aurJ alone, presumably due to spontaneous conversion of YWA1 to nor-rubrofusarin. However, the co-expression of aurZ resulted in an approx. six-fold increase in rubrofusarin production.ConclusionsThe reconstructed pathway for rubrofusarin in S. cerevisiae allows the production of a core scaffold molecule with a branch-point role in several fungal polyketide pathways, thus paving the way for production of further natural pigments and bioactive molecules. Furthermore, the reconstruction verifies the suggested pathway, and as such, it is the first example of utilizing a synthetic biological “bottom up” approach for the validation of a complex fungal polyketide pathway.

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Section: Introductionmentioning

confidence: 99%

Reconstruction of the biosynthetic pathway for the core fungal polyketide scaffold rubrofusarin in Saccharomyces cerevisiae

Rugbjerg

Næsby

Mortensen³

et al. 2013

Microb Cell Fact

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“…[7,9,10] Strain and cultivation: The alternarlactam-producing fungus, identified by Dr. Y. C. Song as Alternaria sp. HG1 according to its macro-and micro-graphic morphological characteristics, [27] was isolated from inside the fresh Carex aridula leaves collected in November 2001 from the suburb of Nanjing, China.…”

Section: Methodsmentioning

confidence: 99%

“…[4][5] This observation fundamentalizes that endophytes, as a big special group of microorganisms, are a rich source of functional biomolecules as substantiated by our characterization of new symbiont metabolites with antitumor, [6][7][8] antimicrobial, [9] and immunosuppressive activities. [10] In continuation of our bioassay for the antitumor secondary metabolites from symbiont cultures, the pronounced cytotoxicity against the test cancer cell line was discerned with the extract derived from the culture of Alternaria sp. HG1, a fungus isolated from inside the healthy leave of Carex aridula belonging to the Cyperaceae family.…”

Section: Introductionmentioning

confidence: 99%

Characterization, Synthesis and Self‐Aggregation of (−)‐Alternarlactam: A New Fungal Cytotoxin with Cyclopentenone and Isoquinolinone Scaffolds

Zhang

Jiang

et al. 2010

Chemistry A European J

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(-)-Alternarlactam [(-)-1], a new promising cytotoxin against two human cancer cell lines, was isolated from an endophyte culture and synthesized (along with (+)-1) from readily available starting materials. The absolute configuration, chirality-activity relevance and self-aggregation of (-)-1 were assigned by a combination of synthetic, spectroscopic and computational approaches. The full characterization of the new fungal cytotoxin may provide valuable information in the discovery of new antitumor agents.

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“…Dalesconols A (176, Scheme 11) and B (177, Scheme 11) are the novel immunosuppressive polyiketides characterized from Daldinia eschscholzii, a mantis-associated fungus [56]. Furthermore, compound 177 holds its additional promise for treating Alzheimer's disease [57].…”

Section: Polyphenolsmentioning

confidence: 99%

Symbionts, a promising source of bioactive natural products

2015

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Unprecedented Immunosuppressive Polyketides from Daldinia eschscholzii, a Mantis‐Associated Fungus

Cited by 34 publications

References 20 publications

Reconstruction of the biosynthetic pathway for the core fungal polyketide scaffold rubrofusarin in Saccharomyces cerevisiae

Reconstruction of the biosynthetic pathway for the core fungal polyketide scaffold rubrofusarin in Saccharomyces cerevisiae

Characterization, Synthesis and Self‐Aggregation of (−)‐Alternarlactam: A New Fungal Cytotoxin with Cyclopentenone and Isoquinolinone Scaffolds

Symbionts, a promising source of bioactive natural products

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