A Putative C2H2 Transcription Factor CgTF6, Controlled by CgTF1, Negatively Regulates Chaetoglobosin A Biosynthesis in Chaetomium globosum

Gα signaling pathway as well as the global regulator LaeA were demonstrated to positively regulate the biosynthesis of chaetoglobosin A (ChA), a promising biotic pesticide produced by Chaetomium globosum. Recently, the regulatory function of Zn2Cys6 binuclear finger transcription factor CgcheR that lies within the ChA biosynthesis gene cluster has been confirmed. However, CgcheR was not merely a pathway specific regulator. In this study, we showed that the homologs gene of CgcheR (designated as Cgtf1) regulate ChA biosynthesis and sporulation in C. globosum NK102. More importantly, RNA-seq profiling demonstrated that 1,388 genes were significant differentially expressed as Cgtf1 deleted. Among them, a putative C2H2 transcription factor, named Cgtf6, showed the highest gene expression variation in zinc-binding proteins encoding genes as Cgtf1 deleted. qRT-PCR analysis confirmed that expression of Cgtf6 was significantly reduced in CgTF1 null mutants. Whereas, deletion of Cgtf6 resulted in the transcriptional activation and consequent increase in the expression of ChA biosynthesis gene cluster and ChA production in C. globosum. These data suggested that CgTF6 probably acted as an end product feedback effector, and interacted with CgTF1 to maintain a tolerable concentration of ChA for cell survival.

Deletion of a Rare Fungal PKS CgPKS11 Promotes Chaetoglobosin A Biosynthesis, Yet Defers the Growth and Development of Chaetomium globosum

We previously reported that chaetoglobosin A (ChA) exhibits a great potential in the biocontrol of nematodes and pathogenic fungi. To improve the production of ChA, a CRISPR-Cas9 system was created and applied for eliminating potential competitive polyketide products. One of the polyketide synthase encoding genes, Cgpks11, which is putatively involved in the biosynthesis of chaetoglocin A, was disrupted. Cgpks11 deletion led to the overexpression of the CgcheA gene cluster, which is responsible for ChA biosynthesis, and a 1.6-fold increase of ChA. Transcription of pks-1, a melanin PKS, was simultaneously upregulated. Conversely, the transcription of genes for chaetoglocin A biosynthesis, e.g., CHGG_10646 and CHGG_10649, were significantly downregulated. The deletion also led to growth retardation and seriously impaired ascospore development. This study found a novel regulatory means on the biosynthesis of ChA by CgPKS11. CgPKS11 affects chaetoglobosin A biosynthesis, growth, and development in Chaetomium globosum.

Detection of Chaetomium globosum, Ch. cochliodes and Ch. rectangulare during the Diversity Tracking of Mycotoxin-Producing Chaetomium-like Isolates Obtained in Buildings in Finland

The diversity of Chaetomium-like isolates in buildings in Finland is poorly documented. This paper describes a set of methods for rapid diversity tracking of 42 indoor Chaetomium-like isolates. These isolates were categorized based on their fluorescence emission, ascomatal hair morphology, responses in three bioassays and resistance/sensitivity to the wetting agent Genapol X-080. Thirty-nine toxigenic isolates were identified [Ch. globosum (n = 35), Ch. cochliodes (n = 2) and Ch. rectangulare (n = 2)]. These isolates were identified down to the species level by tef1α gene sequencing. The major toxic substances in the ethanol extracts of the Ch. globosum and Ch. cochliodes strains were chaetoglobosin, chaetoviridin A and C, chaetomugilin D and chaetomin, identified based on HPLC-UV and mass spectrometry data (MS and MS/MS). Ethanol extracts from pure Ch. globosum cultures exhibited a toxicological profile in the boar sperm motility inhibition assay (BSMI), sperm membrane integrity damage assay (SMID) and inhibition of cell proliferation (ICP) assay, similar to that exhibited by pure chaetoglobosin A. Overall, differences in fluorescence, morphology, toxicity profile, mycotoxin production and sensitivity to chemicals were consistent with those in tef1α sequencing results for species identification. The results indicate the presence of Ch. cochliodes and Ch. rectangulare in Finnish buildings, representing a new finding.

Nematicidal metabolites from endophytic fungus Chaetomium globosum YSC5

ABSTRACT Management of nematodes is a very hectic job due to a highly diverse group of organisms. To find lead compounds for new nematicide development, five metabolites (1–5) were isolated from the culture broth of Chaetomium globosum YSC5 and tested for nematicidal activities against the second stage juveniles (J2s) of Meloidogyne javanica. The results revealed that chaetoglobosin A (1), chaetoglobosin B (2) and flavipin (3) exhibited strong adverse effects (91.6, 83.8 and 87.4%, respectively) on J2 mortality at 200 μg/mL with LC50 values of 88.4, 107.7 and 99.2 μg/mL after 72 h, respectively, while 3-methoxyepicoccone (4) and 4,5,6-trihydroxy-7-methylphthalide (5) showed moderate effects (78.0 and 75.5%, respectively) with LC50 values of 124.0 and 131.6 μg/mL, respectively. Furthermore, in pot assay compounds 1 and 2 appeared to be promising metabolites at 200 μg/mL that significantly reduced nematode reproduction and showed a positive influence on plant growth. Our findings could be helpful for development of new potential bio-based pesticides for integrated management of plant-parasitic nematode.