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Mar. Drugs 2014, 12(4), 1815-1838; doi:10.3390/md12041815

Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate

1
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
2
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
*
Author to whom correspondence should be addressed.
Received: 24 December 2013 / Revised: 12 February 2014 / Accepted: 17 February 2014 / Published: 28 March 2014
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Abstract

AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (17) and two known (89) lipopeptides were isolated together with five known polyketides 1014 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A–G (17). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1′-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 114 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 114 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.
Keywords: marine-derived fungus; lipopeptide; penicimutalide; Marfey analysis; polyketide; Penicillium purpurogenum; DES mutagenesis marine-derived fungus; lipopeptide; penicimutalide; Marfey analysis; polyketide; Penicillium purpurogenum; DES mutagenesis
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MDPI and ACS Style

Wu, C.-J.; Li, C.-W.; Cui, C.-B. Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate. Mar. Drugs 2014, 12, 1815-1838.

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