Uncovering secondary metabolite evolution and biosynthesis using gene cluster networks and genetic dereplication

Theobald, Sebastian; Vesth, Tammi C.; Rendsvig, Jakob Kræmmer; Nielsen, Kristian Fog; Riley, Robert; de Abreu, Lucas Magalhães; Salamov, Asaf; Frisvad, Jens Christian; Larsen, Thomas Ostenfeld; Andersen, Mikael Rørdam; Hoof, Jakob Blæsbjerg

doi:10.1038/s41598-018-36561-3

Uncovering secondary metabolite evolution and biosynthesis using gene cluster networks and genetic dereplication

Journal Article · Tue Dec 18 00:00:00 EST 2018 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-018-36561-3· OSTI ID:1619562

; Vesth, Tammi C.; Rendsvig, Jakob Kræmmer; Nielsen, Kristian Fog; Riley, Robert; ; Salamov, Asaf; Frisvad, Jens Christian; ; ;

Abstract

The increased interest in secondary metabolites (SMs) has driven a number of genome sequencing projects to elucidate their biosynthetic pathways. As a result, studies revealed that the number of secondary metabolite gene clusters (SMGCs) greatly outnumbers detected compounds, challenging current methods to dereplicate and categorize this amount of gene clusters on a larger scale. Here, we present an automated workflow for the genetic dereplication and analysis of secondary metabolism genes in fungi. Focusing on the secondary metabolite rich genus Aspergillus , we categorize SMGCs across genomes into SMGC families using network analysis. Our method elucidates the diversity and dynamics of secondary metabolism in section Nigri , showing that SMGC diversity within the section has the same magnitude as within the genus. Using our genome analysis we were able to predict the gene cluster responsible for biosynthesis of malformin, a potentiator of anti-cancer drugs, in 18 strains. To proof the general validity of our predictions, we developed genetic engineering tools in Aspergillus brasiliensis and subsequently verified the genes for biosynthesis of malformin.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1619562

Alternate ID(s):: OSTI ID: 1546636

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 8; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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