Abstract

The polyketide griseofulvin is a natural antifungal compound and research in griseofulvin has been key in establishing our current understanding of polyketide biosynthesis. Nevertheless, the griseofulvin gsf biosynthetic gene cluster (BGC) remains poorly understood in most fungal species, including Penicillium griseofulvum where griseofulvin was first isolated. To elucidate essential genes involved in griseofulvin biosynthesis, we performed third-generation sequencing to obtain the genome of P. griseofulvum strain D-756. Furthermore, we gathered publicly available genome of 11 other fungal species in which gsf gene cluster was identified. In a comparative genome analysis, we annotated and compared the gsf BGC of all 12 fungal genomes. Our findings show no gene rearrangements at the gsf BGC. Furthermore, seven gsf genes are conserved by most genomes surveyed whereas the remaining six were poorly conserved. This study provides new insights into differences between gsf BGC and suggests that seven gsf genes are essential in griseofulvin production.

Highlights

  • Griseofulvin (C17H17Cl1O6) is a natural spirocyclic polyketide compound that is produced by ascomycetes

  • Griseofulvin biosynthetic gene cluster (BGC) were predicted in 11 other fungal species: Penicillium capsulatum, Penicillium coprophilum, Penicillium vulpinum, three P. griseofulvum, two Aspergillus alliaceus, Aspergillus burnettii, X. flabelliformis, and M. echinata, which showed homology to Minimum Information about a Biosynthetic Gene cluster (MIBiG) accession BGC0000070, the reference griseofulvin BGC from P. aethiopicum (Supplementary File S2 and Data S2)

  • This study provides genomic evidence to understand and identify gsf genes involved in griseofulvin biosynthesis among fungal species

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Summary

Introduction

Griseofulvin (C17H17Cl1O6) is a natural spirocyclic polyketide compound that is produced by ascomycetes. This fungistatic was first isolated from Penicillium griseofulvum Dierckx Given the cost of time and energy, one expects that only species that experience such competition would maintain the griseofulvin gene cluster in their genomes. Fungal endophytes such as Xylaria flabelliformis are commonly found within plant tissue and produces griseofulvin as an antifungal against plant pathogenic fungi (Whalley 1996). Species in Genus Penicillium produce many other secondary metabolites in response to environmental changes, and some exometabolites are only expressed under unique circumstances (Frisvad 2014)

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