Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species
Artikel i vetenskaplig tidskrift, 2017

Filamentous fungi produce a wide range of bioactive compounds with important pharmaceutical applications, such as antibiotic penicillins and cholesterol-lowering statins. However, less attention has been paid to fungal secondary metabolites compared to those from bacteria. In this study, we sequenced the genomes of 9 Penicillium species and, together with 15 published genomes, we investigated the secondary metabolism of Penicillium and identified an immense, unexploited potential for producing secondary metabolites by this genus. A total of 1,317 putative biosynthetic gene clusters (BGCs) were identified, and polyketide synthase and non-ribosomal peptide synthetase based BGCs were grouped into gene cluster families and mapped to known pathways. The grouping of BGCs allowed us to study the evolutionary trajectory of pathways based on 6-methylsalicylic acid (6-MSA) synthases. Finally, we cross-referenced the predicted pathways with published data on the production of secondary metabolites and experimentally validated the production of antibiotic yanuthones in Penicillia and identified a previously undescribed compound from the yanuthone pathway. This study is the first genus-wide analysis of the genomic diversity of Penicillia and highlights the potential of these species as a source of new antibiotics and other pharmaceuticals.

Författare

Jens Christian Froslev Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

S. Grijseels

Danmarks Tekniske Universitet (DTU)

Sylvain Prigent

Chalmers, Biologi och bioteknik, Systembiologi

Boyang Ji

Chalmers, Biologi och bioteknik, Systembiologi

Jacques Dainat

Uppsala universitet

K. F. Nielsen

Danmarks Tekniske Universitet (DTU)

J. C. Frisvad

Danmarks Tekniske Universitet (DTU)

M. Workman

Danmarks Tekniske Universitet (DTU)

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Nature Microbiology

2058-5276 (eISSN)

Vol. 2 6

Ämneskategorier

Mikrobiologi

DOI

10.1038/nmicrobiol.2017.44