Glarea lozoyensis (ATCC 20868 = MF5171 = CBS 492.88). Colony on malt-yeast extract agar. Photo by Gerald Bills.

Glarea lozoyensis (ATCC 20868 = MF5171 = CBS 492.88). Conidia developing from aerial hyphae. Photo by Gerald Bills.

Glarea lozoyensis (ATCC 20868 = MF5171 = CBS 492.88). Meristematic conidial mass. Photo by Gerald Bills.

The genome sequence and gene predictions of Glarea lozoyensis were not determined by the JGI, but were downloaded from NCBI and have been published (Li Chen et al., 2013). Please note that this copy of the genome is not maintained by the author and is therefore not automatically updated.

Glarea lozoyensis is an anamorphic species of the Helotiaceae of medical relevance because it produces a family of lipohexapeptides, named pneumocandins, natural antifungals which act by inhibiting fungal β-(1,3)-glucan synthesis. A semisynthetic derivative of pneumocandin B₀, caspofungin acetate, marketed as CANCIDAS™ since 2001, was the first echinocandin antibiotic brought to the market and has provided invaluable contributions to antifungal therapy to treat serious life-threatening fungal infections (Balkovec et al. 2013). Glarea lozoyensis was first isolated from a water sample from Madrid, Spain, in 1985, and its antifungal activity in a yeast cell wall inhibition assay was detected in 1986. The earliest reports of the pneumocandins misidentified the fungus as Zalerion arboricola (Schwartz et al. 1989, Schwartz et al. 1992). The pneumocandin producer was later shown to be very different to authentic Z. arboricola strains (Bills et al. 1999). Analyses of the ITS and 28S rDNA strains from Spain, Argentina and the USA have placed this enigmatic fungi within the order Helotiales where it is thought to be an anamorphic form of Crocicreas or Cyathicula (Peláez et al. 2011).

The G. lozoyensis genome was sequenced, completely assembled and thoroughly annotated (Chen et al. 2013). The menu of about 50 secondary metabolites encoding genes was predicted from the genome, thus providing a greater understanding the complexity of primary and secondary metabolism in fungi from the yet poorly studied Leotiomycetes. The biosynthetic gene cluster responsible for pneumocandin was predicted in silico and identified by core gene glpks4 and glnrps4 knockouts and bioassay experiments. Study of the genome will enable a more detailed functional analysis of pneumocandin biosynthetic pathways and the identification of other antifungal lipohexapeptide pathways in other fungi, of which both will be essential for increasing pneumocandin production and for generating new pneumocandin and echinocandin derivatives via biocombinatorial chemistry approaches.

References

• Youssar L, Grüning BA, Erxleben A, Günther S, Hüttel W. Genome sequence of the fungus Glarea lozoyensis: the first genome sequence of a species from the Helotiaceae family. Eukaryot Cell. 2012 Feb;11(2):250. doi: 10.1128/EC.05302-11. Erratum in: Eukaryot Cell. 2012 Jun;11(6):829. PubMed PMID: 22302591; PubMed Central PMCID: PMC3272893.
• Chen L, Yue Q, Zhang X, Xiang M, Wang C, Li S, Che Y, Ortiz-López FJ, Bills GF, Liu X, An Z. Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis. BMC Genomics. 2013 May 20;14:339. doi: 10.1186/1471-2164-14-339. PubMed PMID: 23688303; PubMed Central PMCID: PMC3672099.
• Schwartz RE, Giacobbe RA, Bland JA, Monaghan RL. L-671,329, a new antifungal agent. I. Fermentation and isolation. J Antibiot (Tokyo). 1989 Feb;42(2):163-7. PubMed PMID: 2647703.
• Schwartz RE, Sesin DF, Joshua H, Wilson KE, Kempf AJ, Goklen KA, Kuehner D, Gailliot P, Gleason C, White R, et al. Pneumocandins from Zalerion arboricola. I. Discovery and isolation. J Antibiot (Tokyo). 1992 Dec;45(12):1853-66. PubMed PMID: 1490876.