An epigenetic modifier induces production of (10′S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla

Juliana R. Gubiani, E. M Kithsiri Wijeratne, Taoda Shi, Angela R. Araujo, Anne E Arnold, Eli Chapman, Leslie Gunatilaka

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Incorporation of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), to a culture broth of the endophytic fungus Phoma sp. nov. LG0217 isolated from Parkinsonia microphylla changed its metabolite profile and resulted in the production of (10′S)-verruculide B (1), vermistatin (2) and dihydrovermistatin (3). When cultured in the absence of the epigenetic modifier, it produced a new metabolite, (S,Z)-5-(3′,4′-dihydroxybutyldiene)-3-propylfuran-2(5H)-one (4) together with nafuredin (5). The structure of 4 was elucidated by spectroscopic analyses and its absolute configuration was determined by application of the modified Mosher's ester method. The absolute structure of (10′S)-verruculide B was determined as 5-[(10′S,2′E,6′E)-10′,11′-dihydroxy-3′,7′,11′-trimethyldodeca-2′,6′-dien-1′-yl]-(3R)-6,8-dihydroxy-3-methylisochroman-1-one (1) with the help of CD and NOE data. Compound 1 inhibited the activity of protein tyrosine phosphatases (PTPs) 1B (PTP1B), Src homology 2-containing PTP 1 (SHP1) and T-cell PTP (TCPTP) with IC50 values of 13.7 ± 3.4, 8.8 ± 0.6, and 16.6 ± 3.8 μM, respectively. Significance of these activities and observed modest selectivity of 1 for SHP1 over PTP1B and TCPTP is discussed.

Original languageEnglish (US)
Pages (from-to)1860-1866
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number6
DOIs
StatePublished - Mar 15 2017

Keywords

  • (10′S)-verruculide B
  • Epigenetic
  • Histone deacetylase inhibitor
  • Phoma sp. nov. LG0217
  • Protein tyrosine phosphatases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'An epigenetic modifier induces production of (10′S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla'. Together they form a unique fingerprint.

  • Cite this