Abstract

The fungal CTG clade comprises a number of well-known yeasts that impact human health or with high biotechnological potential. To further extend the set of molecular tools dedicated to these microorganisms, the initial focus of this study was to develop a mycophenolic acid (MPA) resistance cassette. Surprisingly, while we were carrying out preliminary susceptibility testing experiments in a set of yeast species, Meyerozyma guilliermondii, although not being a MPA producer, was found to be primarily resistant toward this drug, whereas a series of nine related species were susceptible to MPA. Using comparative and functional genomic approaches, we demonstrated that all MPA-susceptible CTG clade species display a single gene, referred to as IMH3.1, encoding the MPA target inosine monophosphate dehydrogenase (IMPDH) and that MPA resistance relies on the presence in the M. guilliermondii genome of an additional IMPDH-encoding gene (IMH3.2). The M. guilliermondii IMH3.2 gene displays marked differences compared to IMH3.1 including the lack of intron, a roughly 160-fold higher transcription level and a serine residue at position 251. Placed under the control of the M. guilliermondii actin 1 gene promoter, IMH3.2 was successfully used to transform Lodderomyces elongisporus, Clavispora lusitaniae, Scheffersomyces stipitis and Candida parapsilosis.Deciphering molecular mechanisms underlying mycophenolic acid resistance in Meyerozyma guilliermondii shed light on a new selectable marker for fungal CTG clade yeasts genetics.Deciphering molecular mechanisms underlying mycophenolic acid resistance in Meyerozyma guilliermondii shed light on a new selectable marker for fungal CTG clade yeasts genetics.

Keywords

mycophenolic acid; drug resistance; selectable marker; fungi

Published in

FEMS Yeast Research
2016, Volume: 16, number: 6, article number: fow078
Publisher: OXFORD UNIV PRESS

SLU Authors

• Linder, Tomas

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    

Sustainable Development Goals

SDG3 Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Microbiology
Biochemistry and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1093/femsyr/fow078

Permanent link to this page (URI)

https://res.slu.se/id/publ/80495