The chemistry and biology of cytochalasans

Scherlach, Kirstin; Boettger, Daniela; Remme, Nicole; Hertweck, Christian

doi:10.1039/b903913a

Cited by 348 publications

(392 citation statements)

References 154 publications

(194 reference statements)

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“…1A; tetra-, penta-, and heptaketides). Similar trans-acting ERs have also been reported in other fungi such as MokE in Monascus pilosus (8), MlcG in Penicillium citrinum (9), ApdC in Aspergilus nidulans (10-12), cytochalasans (12,13), and tenellin_ORF3 in Beauveria bassiana (14). These trans-acting ERs are highly homologous (38-80% sequence identity; Fig.…”

mentioning

confidence: 63%

Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

Ames

Nguyen

Bruegger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Lovastatin is an important statin prescribed for the treatment and prevention of cardiovascular diseases. Biosynthesis of lovastatin uses an iterative type I polyketide synthase (PKS). LovC is a trans-acting enoyl reductase (ER) that specifically reduces three out of eight possible polyketide intermediates during lovastatin biosynthesis. Such trans-acting ERs have been reported across a variety of other fungal PKS enzymes as a strategy in nature to diversify polyketides. How LovC achieves such specificity is unknown. The 1.9-Å structure of LovC reveals that LovC possesses a medium-chain dehydrogenase/reductase (MDR) fold with a unique monomeric assembly. Two LovC cocrystal structures and enzymological studies help elucidate the molecular basis of LovC specificity, define stereochemistry, and identify active-site residues. Sequence alignment indicates a general applicability to trans-acting ERs of fungal PKSs, as well as their potential application to directing biosynthesis.

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mentioning

confidence: 63%

Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

Ames

Nguyen

Bruegger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Extra domains, MT, ER, KR, and a PCP domain which adds tryptophan to the polyketide backbone in CheA, are missing in PKS-1. A TE domain in PKS-1, which is involved in the release of the polyketide chain, is not present in CheA [15]. We also searched the flanking regions of pks-1, but no comparable gene cluster was found in C. globosum.…”

Section: Discussionmentioning

confidence: 99%

“…We also searched the flanking regions of pks-1, but no comparable gene cluster was found in C. globosum. Chaetoglobosins consists of a polyketide backbone attached to tryptophan group [14,15]; therefore, PKS-1 alone can not complete the entire biosynthetic process. PKS-1 may also affect the biosynthesis of another secondary metabolite in C. globosum as shown by HPLC ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

“…Chaetoglobosin A (CheA) is the most abundant secondary metabolite made by C. globosum and has been investigated for its strong cytotoxicity to tumor cells, antibacterial and antifungal activities [13]. The chemical structure of chaetoglobosin A consists of a polyketide backbone that is condensed from nine units of acetate/malonate, and has a tryptophan residue attached to the cyclized backbone [14,15].…”

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confidence: 99%

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A PKS gene, pks-1, is involved in chaetoglobosin biosynthesis, pigmentation and sporulation in Chaetomium globosum

Hao

Lou

et al. 2012

Sci. China Life Sci.

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Chaetomium globosum is one of the most common fungi in nature. It is best known for producing chaetoglobosins; however, the molecular basis of chaetoglobosin biosynthesis is poorly understood in this fungus. In this study, we utilized RNA interference (RNAi) to characterize a polyketide synthase gene, pks-1, in C. globosum that is involved in the production of chaetoglobosin A. When pks-1 was knocked down by RNAi, the production of chaetoglobosin A dramatically decreased. Knock-down mutants also displayed a pigment-deficient phenotype. These results suggest that the two polyketides, melanin and chaetoglobosin, are likely to share common biosynthetic steps. Most importantly, we found that pks-1 also plays a critical role in sporulation. The silenced mutants of pks-1 lost the ability to produce spores. We propose that polyketides may modulate cellular development via an unidentified action. We also suggest that C. globosum pks-1 is unique because of its triple role in melanin formation, chaetoglobosin biosynthesis and sporulation. This work may shed light on chaetoglobosin biosynthesis and indicates a relationship between secondary metabolism and fungal morphogenesis.

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“…Reportedly, chaetoglobosins, such as chaetoglobosin A (1), were known as cytochalasan alkaloids exhibits strong cytotoxicity on various of human cancer cell lines [17,23]. .…”

Section: In Vitro Antifungal Activity Of Isolated Compoundsmentioning

confidence: 99%

Antifungal Metabolites Produced by Chaetomium globosum No.04, an Endophytic Fungus Isolated from Ginkgo biloba

Zhang

Qin

et al. 2013

Indian J Microbiol

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The fungal endophyte Chaetomium globosum No.04 was isolated from the medicinal plant Ginkgo biloba. The crude extract of the fungus fermentation were active in the agar-diffusion tests against the phytopathogenic fungi Rhizopus stolonifer and Coniothyrium diplodiella. Further bioassay-guided chemical investigation led to the isolation and purification of six alkaloids and three non-targeted compounds from 50 L fermentation of this endophytic fungus and their structures were elucidated as chaetoglobosin A, C, D, E, G, R (1-6), ergosterol, allantoin and uracil, by means of spectroscopic analysis. Compounds 1-6 showed significant growth inhibitory activity against R. stolonifer and C. diplodiella at a concentration of 20 lg/disc. We present here, for the first time, the potent antifungal activity of chaetoglobosins from endophytic fungi against two important phytopathogenic fungi R. stolonifer and C. diplodiella.

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The chemistry and biology of cytochalasans

Cited by 348 publications

References 154 publications

Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

A PKS gene, pks-1, is involved in chaetoglobosin biosynthesis, pigmentation and sporulation in Chaetomium globosum

Antifungal Metabolites Produced by Chaetomium globosum No.04, an Endophytic Fungus Isolated from Ginkgo biloba

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