Structure Elucidation and Antimalarial Activity of Apicidin F: An Apicidin-like Compound Produced by <i>Fusarium fujikuroi</i>

Apicidins are cyclic tetrapeptides with histone deacetylase inhibitory activity. Since their discovery in 1996 a multitude of studies concerning the activity against protozoa and certain cancer cell lines of natural and synthetic apicidin analogues have been published. Until now, the only published natural sources of apicidin are the fungus <i>Fusarium pallidoroseum</i>, later known as <i>F. semitectum</i> and two unspecified <i>Fusarium</i> strains. The biosynthetic origin of apicidins could be associated with a gene cluster, and a biosynthetic pathway has been proposed. Recently, our group was able to identify for the first time an apicidin-like gene cluster in <i>F. fujikuroi</i> that apparently does not lead to the production of any known apicidin analogue. By overexpressing the pathway-specific transcription factor we were able to identify a new apicidin-like compound. The present study provides the complete structure elucidation of the new compound, named apicidin F. Activity evaluation against <i>Plasmodium falciparum</i> showed good in vitro activity with an IC₅₀ value of 0.67 μM

Isolation and Structure Elucidation of Fujikurins A–D: Products of the PKS19 Gene Cluster in <i>Fusarium fujikuroi</i>

<i>Fusarium fujikuroi</i> is a member of the <i>Gibberella fujikuroi</i> species complex and well known for the production of gibberellins and mycotoxins including fusarins and fusaric acid. A recent genome sequencing study revealed that the fungus has the genetic potential to produce many more secondary metabolites than have been reported. This paper describes the structure elucidation of the products of the cryptic and silent PKS19 gene cluster that were recently identified (fujikurins A–D). We present the complete NMR data for the structure elucidation of the main compound fujikurin D, which shows tautomeric 1,3-diketo elements. The different tautomeric structures could be confirmed using quantum chemical calculations. Additionally, the structures of the minor compounds fujikurins A–C were elucidated by high-resolution mass spectrometric fragmentation experiments. It emerged that fujikurin A was identical to the bioactive compound CR377 of the taxonomically unclassified <i>Fusarium</i> strain CR377, while fujikurins B–D have not been reported from other fungi

Structure elucidation and antimalarial activity of apicidin F : an apicidin-like compound produced by Fusarium fujikuroi

Apicidins are cyclic tetrapeptides with histone deacetylase inhibitory activity. Since their discovery in 1996 a multitude of studies concerning the activity against protozoa and certain cancer cell lines of natural and synthetic apicidin analogues have been published. Until now, the only published natural sources of apicidin are the fungus Fusarium pallidoroseum, later known as F. semitectum and two unspecified Fusarium strains. The biosynthetic origin of apicidins could be associated with a gene cluster, and a biosynthetic pathway has been proposed. Recently, our group was able to identify for the first time an apicidin-like gene cluster in F. fujikuroi that apparently does not lead to the production of any known apicidin analogue. By overexpressing the pathway-specific transcription factor we were able to identify a new apicidin-like compound. The present study provides the complete structure elucidation of the new compound, named apicidin F. Activity evaluation against Plasmodium falciparum showed good in vitro activity with an IC50 value of 0.67 μM