Functional and evolutionary characterization of a secondary metabolite gene cluster in budding yeasts

Krause, David J.; Kominek, Jacek; Opulente, Dana A.; Shen, Xing-Xing; Zhou, Xiaofan; Langdon, Quinn K.; DeVirgilio, Jeremy; Hulfachor, Amanda Beth; Kurtzman, Cletus P.; Rokas, Antonis; Hittinger, Chris Todd

doi:10.1073/pnas.1806268115

Title: Functional and evolutionary characterization of a secondary metabolite gene cluster in budding yeasts

Journal Article · 07 October 2018 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.1806268115 · OSTI ID:1506646

Krause, David J. ^[1]; Kominek, Jacek ^[2]; Opulente, Dana A. ^[2]; Shen, Xing-Xing ^[3]; Zhou, Xiaofan ^[3]; Langdon, Quinn K. ^[2]; DeVirgilio, Jeremy ^[4]; Hulfachor, Amanda Beth ^[2]; Kurtzman, Cletus P. ^[4];

^[3];

^[2]

Univ. of Wisconsin, Madison, WI (United States); University of Wisconsin-Madison Laboratory of Genetics
Univ. of Wisconsin, Madison, WI (United States)
Vanderbilt Univ., Nashville, TN (United States)
US Department of Agriculture, Peoria, IL (United States)

Secondary metabolites are key in how organisms from all domains of life interact with their environment and each other. The iron-binding molecule pulcherrimin was described a century ago, but the genes responsible for its production in budding yeasts have remained uncharacterized. In this study, we used phylogenomic footprinting on 90 genomes across the budding yeast subphylum Saccharomycotina to identify the gene cluster associated with pulcherrimin production. Using targeted gene replacements in Kluyveromyces lactis, we characterized the four genes that make up the cluster, which likely encode two pulcherriminic acid biosynthesis enzymes, a pulcherrimin transporter, and a transcription factor involved in both biosynthesis and transport. The requirement of a functional putative transporter to utilize extracellular pulcherrimin-complexed iron demonstrates that pulcherriminic acid is a siderophore, a chelator that binds iron outside the cell for subsequent uptake. Surprisingly, we identified homologs of the putative transporter and transcription factor genes in multiple yeast genera that lacked the biosynthesis genes and could not make pulcherrimin, including the model yeast Saccharomyces cerevisiae. We deleted these previously uncharacterized genes and showed they are also required for pulcherrimin utilization in S. cerevisiae, raising the possibility that other genes of unknown function are linked to secondary metabolism. Lastly, phylogenetic analyses of this gene cluster suggest that pulcherrimin biosynthesis and utilization were ancestral to budding yeasts, but the biosynthesis genes and, subsequently, the utilization genes, were lost in many lineages, mirroring other microbial public goods systems that lead to the rise of cheater organisms.

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Research Organization:: Great Lakes Bioenergy Research Center, Madison, WI (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Contributing Organization:: University of Wisconsin Biotechnology Center

Grant/Contract Number:: FC02-07ER64494; SC0018409

OSTI ID:: 1506646

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 43 Vol. 115; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

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