A synthesis of endocrocin, endocrocin-9-anthrone, and related compounds

Steglich, Wölfgang; Reininger, W.

doi:10.1039/c2970000178a

Cited by 13 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that overexpression of the encA transcript resulted in higher transcript levels of encA-D and higher production of endocrocin. We discuss a model of the enc cluster as one evolutionary origin of fungal anthraquinones derived from a nonreducing polyketide synthase and a discrete metallo-␤-lactamase-type thioesterase.T he anthraquinone endocrocin was first described in 1935 from the lichen Nephromopsis endocrocea and since has been isolated from various fungi (16,26,30,37), insects (22), and plants (17). Endocrocin and related anthraquinones are noted for their industrial uses as dyes, food additives, components of paper making, and cosmetics (18) as well as for their medicinal uses, including as laxative, anti-inflammatory, and antitumor agents (17,19).…”

mentioning

confidence: 99%

Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

Lim

Hou

Chen

et al. 2012

Appl Environ Microbiol

View full text Add to dashboard Cite

ABSTRACTEndocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. Several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major metabolite has been identified. Here we describe our biosynthetic and regulatory characterization of the endocrocin gene cluster inAspergillus fumigatus. This is the first report of this anthraquinone in this species. The biosynthetic genes required for endocrocin production are regulated by the global regulator of secondary metabolism, LaeA, and encode an iterative nonreducing polyketide synthase (encA), a physically discrete metallo-β-lactamase type thioesterase (encB), and a monooxygenase (encC). Interestingly, the deletion of a gene immediately adjacent toencC, termedencDand encoding a putative 2-oxoglutarate-Fe(II) type oxidoreductase, resulted in higher levels of endocrocin production than in the wild-type strain, whereas overexpression ofencDeliminated endocrocin accumulation. We found that overexpression of theencAtranscript resulted in higher transcript levels ofencA-Dand higher production of endocrocin. We discuss a model of theenccluster as one evolutionary origin of fungal anthraquinones derived from a nonreducing polyketide synthase and a discrete metallo-β-lactamase-type thioesterase.

show abstract

mentioning

confidence: 99%

Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

Lim

Hou

Chen

et al. 2012

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…The aptC deletion mutant did not produce any major compound detectable at a UV wavelength of 254 nm (see Fig. S3 in the supplemental material) since endocrocin-9-anthrone is known to be unstable in solution (22) and probably decomposed during the extraction process.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the Asperthecin Gene Cluster of Aspergillus nidulans

Szewczyk

Chiang

Oakley

et al. 2008

Appl Environ Microbiol

155

165

View full text Add to dashboard Cite

The sequencing of Aspergillus genomes has revealed that the products of a large number of secondary metabolism pathways have not yet been identified. This is probably because many secondary metabolite gene clusters are not expressed under normal laboratory culture conditions. It is, therefore, important to discover conditions or regulatory factors that can induce the expression of these genes. We report that the deletion of sumO, the gene that encodes the small ubiquitin-like protein SUMO in A. nidulans, caused a dramatic increase in the production of the secondary metabolite asperthecin and a decrease in the synthesis of austinol/ dehydroaustinol and sterigmatocystin. The overproduction of asperthecin in the sumO deletion mutant has allowed us, through a series of targeted deletions, to identify the genes required for asperthecin synthesis. The asperthecin biosynthesis genes are clustered and include genes encoding an iterative type I polyketide synthase, a hydrolase, and a monooxygenase. The identification of these genes allows us to propose a biosynthetic pathway for asperthecin.Secondary metabolites are a remarkably rich source of medically useful compounds. A survey of the literature on 1,500 secondary metabolites isolated and characterized between 1993 and 2001 revealed that over half of these compounds have antibacterial, antifungal, or antitumor activity (19). Fungal secondary metabolites, in particular, include a number of important compounds, such as penicillin, cephalosporin, the antihypercholesterolemic agent lovastatin and other statins, and immunosuppressants such as cyclosporine, as well as antifungals (reviewed in references 3, 13, 16, and 19). Other fungal secondary metabolites are important not for their benefits but rather for the problems they cause. For example, the carcinogenic toxins aflatoxin and sterigmatocystin are produced by members of the genus Aspergillus (see references 7, 28, and 29 and earlier references therein; reviewed additionally in references 1 and 26).The sequencing of fungal genomes has revealed several important things about fungal secondary metabolism. First, as was suspected from the results of previous work (13), the genes of pathways that produce particular secondary metabolites are often clustered together (10, 14, 18). Second, fungi have many more secondary metabolism pathways than was previously thought. Analyses of the A. nidulans genome, for example, indicate that A. nidulans has 50 clusters that are predicted to synthesize secondary metabolites (27 polyketides, 14 nonribosomal peptides, 6 fatty acids, 1 terpene, and 2 indole alkaloids) (3, 18). Our own genomic analyses suggest that this number may be a slight overestimate (because more than one polyketide synthase [PKS] and/or nonribosomal peptide synthetase may be involved in a single pathway), but clearly A. nidulans has the ability to synthesize many secondary metabolites. Only a limited number of secondary metabolites in A. nidulans have been identified (aspyridones A and B [from a single pathway], aspoqui...

show abstract

ChemInform Abstract: DARST. VON ENDOCROCIN, ENDOCROCIN‐9‐ANTHRON UND VERWANDTEN VERBINDUNGEN

Steglich¹,

Reininger²

1970

Chemischer Informationsdienst. Organische Chemie

View full text Add to dashboard Cite

show abstract

A synthesis of endocrocin, endocrocin-9-anthrone, and related compounds

Abstract: Endocrocin-9-anthrone and endocrocin, the biogenetic precursors of emodin-type anthraquinones, have been synthesized by a method easily adaptable to the synthesis of radioactively labelled compounds.

Cited by 13 publications

References 0 publications

Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

Identification and Characterization of the Asperthecin Gene Cluster of Aspergillus nidulans

ChemInform Abstract: DARST. VON ENDOCROCIN, ENDOCROCIN‐9‐ANTHRON UND VERWANDTEN VERBINDUNGEN

Contact Info

Product

Resources

About