|Chang, Perng Kuang
Submitted to: Applied Microbiology and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/18/2013
Publication Date: 6/6/2013
Publication URL: http://handle.nal.usda.gov/10113/56906
Citation: Chang, P.-K., Ehrlich, K. 2013. Genome-wide analysis of the Zn(II)2Cys6 zinc cluster-encoding gene family in Aspergillus flavus. Applied Microbiology and Biotechnology. 97(10):4289-4300.
Interpretive Summary: Aspergillus flavus is a saprophytic soil fungus that can produce the carcinogenic aflatoxin. It is the second-leading causative agent of invasive aspergillosis. The 37-Mb genome of A. flavus contains 12,000 genes. However, knowledge regarding the zinc-cluster family genes that encode DNA-binding regulatory proteins which are vital to many cellular processes and involved in secondary metabolism is still scarce. In this article, combining manual and automatic annotations has provided a complete overview of the total number, structure, and subgroups of this genes family. Two and a half percent of the predicted total proteins are estimated to be zinc-cluster proteins. Of the 55 predicted gene clusters thought to be involved in production of secondary metabolites about half have a C6-encoding gene in or near the gene clusters. The review also indicates that refined bioinformatic algorithms are urgently needed to accurately annotate this gene family in other fungal genomes.
Technical Abstract: Proteins with a Zn(II)2Cys6 domain, Cys-X2-Cys-X6-Cys-X5-12-Cys-X2-Cys-X6-9-Cys (hereafter, referred to as the C6 domain), form a subclass of zinc finger proteins found exclusively in fungi and yeast. Genome sequence databases of Saccharomyces cerevisiae and Candida albicans have provided an overview of this family of genes. Annotation of this gene family in most fungal genomes is still far from perfect and refined bioinformatic algorithms are urgently needed. Aspergillus flavus is a saprophytic soil fungus that can produce the carcinogenic aflatoxin. It is the second-leading causative agent of invasive aspergillosis. The 37 Mb genome of A. flavus is predicted to encode 12,000 proteins. Two and a half percent of the total proteins are estimated to contain the C6 domain, more than two-fold greater than those estimated for yeast, which is about one percent. The variability in the spacing between cysteines, C3 -C4 and C5-C6, in the zinc cluster enables classification of the domains into distinct subgroups, which are also well-conserved in A. nidulans. Sixty-six percent (202/306) of the A. flavus C6 proteins contain a specific transcription factor domain, and seven percent contain a specific domain of unknown function, DUF3468. Two A. nidulans C6 proteins containing the DUF3468 are involved in asexual conidiation and another two in sexual differentiation. In the anamorphic A. flavus, only homologs of the former are DUF3468 proteins. Of the 55 predicted gene clusters thought to be involved in production of secondary metabolites only about half have a C6-encoding gene in or near the gene clusters. The features revealed by the A. flavus C6 proteins likely are common for other ascomycete fungi.