Stereo- and Region-specific Biotransformation of Physapubescin by Four Fungal Strains

Overview

Journal J Nat Med

Publisher Springer

Date 2017 Jan 12

PMID 28074432

Authors

Chongyue Qiu

Ting Yuan

Dejuan Sun

Suyu Gao

Lixia Chen

Affiliations

Soon will be listed here.

Abstract

Biotransformations of physapubescin (1) were performed by four fungal strains-Mucor subtilissimus AS 3.2454, Mucor polymorphosporus AS 3.3443, Aspergillus niger AS 3.795, and Syncephalastrum racemosum AS 3.264. Four metabolites were prepared in the biotransformation process of 1, and their structures were elucidated as 15α-acetoxy-5,6β:22,26:24,25-triepoxy-26α-hydroxy-3β-methoxy 4β-hydroxyergost-1-one (2), 15α-acetoxy-5,6β:22,26-diepoxy-4β,24β,25α,26(α, β)-tetrahydroxyergost-3β-methoxy-1-one (3a/3b), 15α-acetoxy-5,6β:22,26-diepoxy-4β,24β,25α,26(α, β)-tetrahydroxyergost-2-en-1-one (4a/4b), and physapubescin D (5), by spectroscopic data analysis. Among them, metabolites 2 and 3 are new. All of these fungal strains showed the ability to be highly stereo- and region-specific for the bioconversion of substrate (1). Our research provides a reference for the structural derivatization of withanolides or possibly even other natural products.

References

Cao C, Wu X, Kindscher K, Xu L, Timmermann B . Withanolides and Sucrose Esters from Physalis neomexicana. J Nat Prod. 2015; 78(10):2488-93. DOI: 10.1021/acs.jnatprod.5b00698. View

Sun C, Qiu C, Yuan T, Nie X, Sun H, Zhang Q . Antiproliferative and Anti-inflammatory Withanolides from Physalis angulata. J Nat Prod. 2016; 79(6):1586-97. DOI: 10.1021/acs.jnatprod.6b00094. View

Chen L, Xia G, Qiu F, Wu C, Denmon A, Zi X . Physapubescin selectively induces apoptosis in VHL-null renal cell carcinoma cells through down-regulation of HIF-2α and inhibits tumor growth. Sci Rep. 2016; 6:32582. PMC: 5007653. DOI: 10.1038/srep32582. View

Tettamanzi , Veleiro , Oberti , Burton . New Hydroxylated Withanolides from Salpichroa origanifolia. J Nat Prod. 1998; 61(3):338-42. DOI: 10.1021/np970387s. View

Yang Y, Xie S, Xu W, Nian Y, Liu X, Peng X . Six new physalins from Physalis alkekengi var. franchetii and their cytotoxicity and antibacterial activity. Fitoterapia. 2016; 112:144-52. DOI: 10.1016/j.fitote.2016.05.010. View

Lv X, Liu D, Hou J, Dong P, Zhan L, Wang L . Biotransformation of imperatorin by Penicillium janthinellum. Anti-osteoporosis activities of its metabolites. Food Chem. 2013; 138(4):2260-6. DOI: 10.1016/j.foodchem.2012.11.138. View

Chen L, He H, Qiu F . Natural withanolides: an overview. Nat Prod Rep. 2011; 28(4):705-40. DOI: 10.1039/c0np00045k. View

Basso A, Nicotra V, Parra A, Martinez A, Fernandez-Vivas A . Biotransformation of Salpichrolides A, C, and G by Three Filamentous Fungi. J Nat Prod. 2016; 79(6):1658-67. DOI: 10.1021/acs.jnatprod.6b00310. View

He H, Zang L, Feng Y, Chen L, Kang N, Tashiro S . Physalin A induces apoptosis via p53-Noxa-mediated ROS generation, and autophagy plays a protective role against apoptosis through p38-NF-κB survival pathway in A375-S2 cells. J Ethnopharmacol. 2013; 148(2):544-55. DOI: 10.1016/j.jep.2013.04.051. View

10.

Xia G, Li Y, Sun J, Wang L, Tang X, Lin B . Withanolides from the stems and leaves of Physalis pubescens and their cytotoxic activity. Steroids. 2016; 115:136-146. DOI: 10.1016/j.steroids.2016.09.002. View

11.

Cao C, Zhang H, Gallagher R, Timmermann B . Withanolide artifacts formed in methanol. J Nat Prod. 2013; 76(11):2040-6. DOI: 10.1021/np400296s. View

12.

Sang-Ngern M, Youn U, Park E, Kondratyuk T, Simmons C, Wall M . Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity. Bioorg Med Chem Lett. 2016; 26(12):2755-2759. DOI: 10.1016/j.bmcl.2016.04.077. View

13.

Xu Q, Liu Y, Feng Y, Li X, Yang S . C28 sterols with a cyclopentane ring at C-22 and 26 from cape gooseberry (berries of Physalis pubeacens L.). J Asian Nat Prod Res. 2010; 12(9):752-9. DOI: 10.1080/10286020.2010.497657. View

14.

Chen L, Xia G, He H, Huang J, Qiu F, Zi X . New withanolides with TRAIL-sensitizing effect from L. RSC Adv. 2016; 6(58):52925-52936. PMC: 5095689. DOI: 10.1039/C6RA07031K. View

15.

Peng C, You B, Lee C, Wu Y, Lin W, Lu T . The Roles of 4β-Hydroxywithanolide E from Physalis peruviana on the Nrf2-Anti-Oxidant System and the Cell Cycle in Breast Cancer Cells. Am J Chin Med. 2016; 44(3):617-36. DOI: 10.1142/S0192415X16500348. View

16.

Ji L, Yuan Y, Ma Z, Chen Z, Gan L, Ma X . Induction of quinone reductase (QR) by withanolides isolated from Physalis pubescens L. (Solanaceae). Steroids. 2013; 78(9):860-5. DOI: 10.1016/j.steroids.2013.05.008. View

17.

Zhu X, Takagi M, Ikeda T, Midzuki K, Nohara T . Withanolide-type steroids from Solanum cilistum. Phytochemistry. 2001; 56(7):741-5. DOI: 10.1016/s0031-9422(00)00487-8. View

18.

Ma Y, Han W, Li J, Hu L, Zhou Y . Physalin B not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in human colon cancer cells in vitro. Acta Pharmacol Sin. 2015; 36(4):517-27. PMC: 4387302. DOI: 10.1038/aps.2014.157. View

19.

Kumar S, Seal C, Howes M, Kite G, Okello E . In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and β-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells. Phytother Res. 2010; 24(10):1567-74. DOI: 10.1002/ptr.3261. View

20.

Siddique A, Joshi P, Misra L, Sangwan N, Darokar M . 5,6-de-epoxy-5-en-7-one-17-hydroxy withaferin A, a new cytotoxic steroid from Withania somnifera L. Dunal leaves. Nat Prod Res. 2014; 28(6):392-8. DOI: 10.1080/14786419.2013.871545. View