Nodulisporiviridins A–H, Bioactive Viridins from <i>Nodulisporium</i> sp.

Zhao, Qing; Chen, Guodong; Xu, Feng; Yu, Yang; He, Rong‐Rong; Li, Xiaoxia; Yan, Huang; Zhou, Wen; Guo, Liangdong; Zheng, Youliang; Yao, Xin‐Sheng; Gao, Hao

doi:10.1021/np500912t

Cited by 55 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(no. 65-12-7-1), which can produce large amounts of demethoxyviridin ( 1 ) and several analogs 25 , 26 . These findings provided a good chance to elucidate its biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage

et al. 2018

Self Cite

View full text Add to dashboard Cite

Furanosteroids, represented by wortmannin, viridin, and demethoxyviridin, are a special group of fungal-derived, highly oxygenated steroids featured by an extra furan ring. They are well-known nanomolar-potency inhibitors of phosphatidylinositol 3-kinase and widely used in biological studies. Despite their importance, the biosyntheses of these molecules are poorly understood. Here, we report the identification of the biosynthetic gene cluster for demethoxyviridin, consisting of 19 genes, and among them 15 biosynthetic genes, including six cytochrome P450 monooxygenase genes, are deleted. As a result, 14 biosynthetic intermediates are isolated, and the biosynthetic pathway for demethoxyviridin is elucidated. Notably, the pregnane side-chain cleavage requires three enzymes: flavin-dependent Baeyer-Villiger monooxygenase, esterase, and dehydrogenase, in sharp contrast to the single cytochrome P450-mediated process in mammalian cells. Structure–activity analyses of these obtained biosynthetic intermediates reveal that the 3-keto group, the C1β–OH, and the aromatic ring C are important for the inhibition of phosphatidylinositol 3-kinase.

show abstract

“…(no. 65-12-7-1), which can produce large amounts of demethoxyviridin ( 1 ) and several analogs 25 , 26 . These findings provided a good chance to elucidate its biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…(No. 65-12-7-1) 21 , 22 . Most of these compounds exhibited substantial anti-Alzheimer’s disease activity.…”

Section: Introductionmentioning

confidence: 99%

Development of a versatile and conventional technique for gene disruption in filamentous fungi based on CRISPR-Cas9 technology

Zheng

Lin

Gao

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Filamentous fungi represent an invaluable source of pharmaceutically active compounds. The development of versatile methods to genetically manipulate filamentous fungi is of great value for improving the low yields of bioactive metabolites and expanding chemical diversity. The CRISPR-Cas9-based system has become a common platform for genome editing in a variety of organisms. However, recent application of this technology in filamentous fungi is limited to model strains, a versatile method for efficient gene disruption in different fungi is lacking. Here, we investigated the utility of the CRISPR-Cas9 system in a less-studied fungus Nodulisporium sp. (No. 65-12-7-1), and we have developed an efficient CRISPR-Cas9-based gene disruption strategy by simultaneous transformation of in vitro transcriptional gRNA and the linear maker gene cassette into the Cas9-expressing fungi. We found that the linear marker gene cassette could not only allow for selection of transformants, but also significantly enhance the gene disruption efficiency by inserting itself into the Cas9 cut site. Moreover, the above approach also demonstrated its efficiency in two other phylogenetically distinct strains Aspergillus oryzae NSAR1 and Sporormiella minima (No. 40-1-4-1) from two different classes of Ascomycota. These results suggested that a versatile CRISPR-Cas9-based gene disruption method in filamentous fungi was established.

show abstract

“…Bioassay screening of these alkaloids showed anxiolytic-like actitivity [3], induced sleep [4], anticonvulsant actitivity [5], neuronal nicotinic acetylcholine receptor antagonism [6], leishmanicidal [7], anticataract [7], and antifeedant activity [8]. Our previous research disclosed natural dimeric [9,10] and trimeric [11] Erythrina alkaloids, alkaloidal glucosides [10], and complex monomers [12][13][14]. However, during the extraction and separation of Erythrina alkaloids, some artificial products would be produced.…”

Section: Introductionmentioning

confidence: 99%

Artificial Erythrina Alkaloids from Three Erythrina Plants, E. variegata, E. crista-galli and E. arborescens

Zhang

Bao

et al. 2020

Nat. Prod. Bioprospect.

View full text Add to dashboard Cite

Fourteen unprecedented artificial Erythrina alkaloids were isolated from the Erythrina variegata, E. crista-galli and E. arborescens (Fabaceae). The structures of these alkaloids were determined by spectroscopic analyses. Their possible formations were proposed. All isolated compounds showed no cytotoxicity and hypoglycemic activity at cell screening bioassay.Alkaloid 1 was obtained as white amorphous powder. Its IR absorption bands at 3441, 1640, 1503, 1480 cm −1 indicated the presence of the hydroxyls and aromatic rings. Moreover, the UV absorptions at 204, 239 and 290 nm indicated a tetrahydroisoquinoline chromophore [15]. These spectra were consistent with the characteristics of an Erythrina alkaloid. Alkaloid 1 had a molecular formula C 39 H 40 N 2 O 9 as established by the HRESIMS m/z at 681.2811 [M+H] + , together with the 1 H and 13 C NMR spectroscopic data. In the 1 H NMR spectrum of 1 (Table 1), four aromatic singlet proton (δ H 7.08, 7.01, 6.74 × 2), two pairs of olefin [δ H 7.16 (dd, J = 10.2, 4.2 Hz), 5.92 (d, J = 10.2 Hz), and 6.56 (dd, J = 10.2, 2.4 Hz), 6.06 (d, J = 10.2 Hz)], two methylenedioxy group (δ H 5.96, 5.94, 5.93 and 5.92), and two methoxyl group (δ H 3.29 and 3.24) signals indicated that 1 might be an Erythrina alkaloid dimer. In comparison with the reported dimer, erythrivarine A [9], alkaloid 1 had three more signals at δ C 208.1, 47.5 and 31.2 in the 13 C NMR spectra and 56 mass units higher in molecular weight, which showed Bing-Jie Zhang and Jing Wu have contributed equally to this work.Dedicated to Professor Han-Dong Sun on the occasion of his 80th birthday.

show abstract

Nodulisporiviridins A–H, Bioactive Viridins from Nodulisporium sp.

Cited by 55 publications

References 27 publications

Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage

Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage

Development of a versatile and conventional technique for gene disruption in filamentous fungi based on CRISPR-Cas9 technology

Artificial Erythrina Alkaloids from Three Erythrina Plants, E. variegata, E. crista-galli and E. arborescens

Contact Info

Product

Resources

About