GNPS-guided Discovery of Xylacremolide C and D, Evaluation of Their Putative Biosynthetic Origin and Bioactivity Studies of Xylacremolide A and B

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 May 28

PMID 34046176

Citations 2

Authors

Felix Schalk

Janis Fricke

Soohyun Um

Benjamin H Conlon

Hannah Maus

Nils Jager

Thorsten Heinzel

Tanja Schirmeister

Michael Poulsen

Christine Beemelmanns

Affiliations

Soon will be listed here.

Abstract

Targeted HRMS-GNPS-based metabolomic analysis of sp. X187, a fungal antagonist of the fungus-growing termite symbiosis, resulted in the identification of two lipopeptidic congeners of xylacremolides, named xylacremolide C and D, which are built from d-phenylalanine, l-proline and an acetyl-CoA starter unit elongated by four malonyl-CoA derived ketide units. The putative gene cluster was identified from a draft genome generated by Illumina and PacBio sequencing and RNAseq studies. Biological activities of xylacremolide A and B were evaluated and revealed weak histone deacetylase inhibitory (HDACi) and antifungal activities, as well as moderate protease inhibition activity across a panel of nine human, viral and bacterial proteases.

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References

Ratnayake R, Fremlin L, Lacey E, Gill J, Capon R . Acremolides A-D, lipodepsipeptides from an Australian marine-derived fungus, Acremonium sp. J Nat Prod. 2008; 71(3):403-8. DOI: 10.1021/np070589g. View

Doyle P, Zhou Y, Hsieh I, Greenbaum D, McKerrow J, Engel J . The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS Pathog. 2011; 7(9):e1002139. PMC: 3164631. DOI: 10.1371/journal.ppat.1002139. View

Monteiro M, de la Cruz M, Cantizani J, Moreno C, Tormo J, Mellado E . A new approach to drug discovery: high-throughput screening of microbial natural extracts against Aspergillus fumigatus using resazurin. J Biomol Screen. 2012; 17(4):542-9. DOI: 10.1177/1087057111433459. View

Vurture G, Sedlazeck F, Nattestad M, Underwood C, Fang H, Gurtowski J . GenomeScope: fast reference-free genome profiling from short reads. Bioinformatics. 2017; 33(14):2202-2204. PMC: 5870704. DOI: 10.1093/bioinformatics/btx153. View

Mori H, Abe F, Furukawa S, Furukawa S, Sakai F, Hino M . FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase (HDAC) II. Biological activities in animal models. J Antibiot (Tokyo). 2003; 56(2):80-6. View

Visser A, Ros V, de Beer Z, Debets A, Hartog E, Kuyper T . Levels of specificity of Xylaria species associated with fungus-growing termites: a phylogenetic approach. Mol Ecol. 2009; 18(3):553-67. DOI: 10.1111/j.1365-294X.2008.04036.x. View

Song F, Wu S, Zhai Y, Xuan Q, Wang T . Secondary metabolites from the genus xylaria and their bioactivities. Chem Biodivers. 2014; 11(5):673-94. DOI: 10.1002/cbdv.201200286. View

Vassaux A, Meunier L, Vandenbol M, Baurain D, Fickers P, Jacques P . Nonribosomal peptides in fungal cell factories: from genome mining to optimized heterologous production. Biotechnol Adv. 2019; 37(8):107449. DOI: 10.1016/j.biotechadv.2019.107449. View

Bankevich A, Nurk S, Antipov D, Gurevich A, Dvorkin M, Kulikov A . SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012; 19(5):455-77. PMC: 3342519. DOI: 10.1089/cmb.2012.0021. View

10.

Kandeel M, Kitade Y, Fayez M, Venugopala K, Ibrahim A . The emerging SARS-CoV-2 papain-like protease: Its relationship with recent coronavirus epidemics. J Med Virol. 2020; 93(3):1581-1588. DOI: 10.1002/jmv.26497. View

11.

Marcais G, Kingsford C . A fast, lock-free approach for efficient parallel counting of occurrences of k-mers. Bioinformatics. 2011; 27(6):764-70. PMC: 3051319. DOI: 10.1093/bioinformatics/btr011. View

12.

Poulsen M, Hu H, Li C, Chen Z, Xu L, Otani S . Complementary symbiont contributions to plant decomposition in a fungus-farming termite. Proc Natl Acad Sci U S A. 2014; 111(40):14500-5. PMC: 4209977. DOI: 10.1073/pnas.1319718111. View

13.

Mazmanian S, Liu G, Jensen E, Lenoy E, Schneewind O . Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections. Proc Natl Acad Sci U S A. 2000; 97(10):5510-5. PMC: 25859. DOI: 10.1073/pnas.080520697. View

14.

Welker A, Kersten C, Muller C, Madhugiri R, Zimmer C, Muller P . Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2. ChemMedChem. 2020; 16(2):340-354. PMC: 7894572. DOI: 10.1002/cmdc.202000548. View

15.

Guo H, Schmidt A, Stephan P, Raguz L, Braga D, Kaiser M . Precursor-Directed Diversification of Cyclic Tetrapeptidic Pseudoxylallemycins. Chembiochem. 2018; 19(21):2307-2311. DOI: 10.1002/cbic.201800503. View

16.

Duffy M, McGowan P, Harbeck N, Thomssen C, Schmitt M . uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res. 2015; 16(4):428. PMC: 4423643. DOI: 10.1186/s13058-014-0428-4. View

17.

Clevenger K, Bok J, Ye R, Miley G, Verdan M, Velk T . A scalable platform to identify fungal secondary metabolites and their gene clusters. Nat Chem Biol. 2017; 13(8):895-901. PMC: 5577364. DOI: 10.1038/nchembio.2408. View

18.

Cullen D, Mocerino M . A Brief Review of Drug Discovery Research for Human African Trypanosomiasis. Curr Med Chem. 2017; 24(7):701-717. DOI: 10.2174/0929867324666170120160034. View

19.

Fukasawa W, Mori N, Iwatsuki M, Hokari R, Ishiyama A, Nakajima M . Tolyprolinol, a new dipeptide from Tolypocladium sp. FKI-7981. J Antibiot (Tokyo). 2018; 71(7):682-684. DOI: 10.1038/s41429-018-0041-3. View

20.

Gareis M, Gottschalk C . Stachybotrys spp. and the guttation phenomenon. Mycotoxin Res. 2014; 30(3):151-9. DOI: 10.1007/s12550-014-0193-3. View