Investigation of chetomin as a lead compound and its biosynthetic pathway

Zhao, Peipei; Liu, Hairong; Wu, Qinghua; Meng, Qingzhou; Qu, Kunyu; Yin, Xin; Wang, Mengmeng; Zhao, Xiangxiang; Qi, Jun; Meng, Yiwei; Xia, Xuekui; Zhang, Lixin

doi:10.1007/s00253-022-11925-y

Cited by 4 publications

(16 citation statements)

References 35 publications

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“…[34] Furthermore, it is a potent antibiotic compound and targets methicillin-resistant Staph-ylococcus aureus (MRSA) with higher potency than vancomycin. [189] Chetomin is also produced by Chaetomium globosum, [190] a species that can infect human skin and nails and ultimately lead to systemic lethal mycoses in immunocompromised patients. [191] Recently, the chetomin biosynthesis gene cluster has been identified in C. cochliodes SD-280.…”

Section: Chetominmentioning

confidence: 99%

“…[191] Recently, the chetomin biosynthesis gene cluster has been identified in C. cochliodes SD-280. [189] It comprises 18 genes, nine of which with enigmatic function in chetomin production. The predicted enzymes CheP, CheG, CheK, CheJ, CheN and CheT likely fulfill similar functions as their homologues from gliotoxin biosynthesis (Figure 10A).…”

Section: Chetominmentioning

confidence: 99%

“…The enzyme TmtA for example, encoded outside the gli gene cluster, was identified to account for the production of bis(methylthio)gliotoxin. [75d,76] Albeit genome mining approaches significantly boostered ETP research during the last two decades, ETP production [189] ORFs are colored according to homology of their products to Gli proteins (see Figure 2A for comparison). Several genes of the common ETP set are present in the cluster (cheP, cheG, cheK, cheJ, cheT), but some are missing (cheI) and many are of unknown function (black ones).…”

Section: Final Considerationsmentioning

confidence: 99%

“…Chetomin acts as an anti‐cancer agent [188] by blocking the interaction of Hif1a and p300 [34] . Furthermore, it is a potent antibiotic compound and targets methicillin‐resistant Staphylococcus aureus (MRSA) with higher potency than vancomycin [189] . Chetomin is also produced by Chaetomium globosum , [190] a species that can infect human skin and nails and ultimately lead to systemic lethal mycoses in immunocompromised patients [191]…”

Section: Epipolythiodioxopiperazines: Bridging the Ringmentioning

confidence: 99%

“…Recently, the chetomin biosynthesis gene cluster has been identified in C. cochliodes SD‐280 [189] . It comprises 18 genes, nine of which with enigmatic function in chetomin production.…”

Section: Epipolythiodioxopiperazines: Bridging the Ringmentioning

confidence: 99%

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Epipolythiodioxopiperazine‐Based Natural Products: Building Blocks, Biosynthesis and Biological Activities

Huber

2022

ChemBioChem

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Epipolythiodioxopiperazines (ETPs) are fungal secondary metabolites that share a 2,5‐diketopiperazine scaffold built from two amino acids and bridged by a sulfide moiety. Modifications of the core and the amino acid side chains, for example by methylations, acetylations, hydroxylations, prenylations, halogenations, cyclizations, and truncations create the structural diversity of ETPs and contribute to their biological activity. However, the key feature responsible for the bioactivities of ETPs is their sulfide moiety. Over the last years, combinations of genome mining, reverse genetics, metabolomics, biochemistry, and structural biology deciphered principles of ETP production. Sulfurization via glutathione and uncovering of the thiols followed by either oxidation or methylation crystallized as fundamental steps that impact expression of the biosynthesis cluster, toxicity and secretion of the metabolite as well as self‐tolerance of the producer. This article showcases structure and activity of prototype ETPs such as gliotoxin and discusses the current knowledge on the biosynthesis routes of these exceptional natural products.

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Section: Chetominmentioning

confidence: 99%

Section: Chetominmentioning

confidence: 99%

Section: Final Considerationsmentioning

confidence: 99%

Section: Epipolythiodioxopiperazines: Bridging the Ringmentioning

confidence: 99%

“…Recently, the chetomin biosynthesis gene cluster has been identified in C. cochliodes SD‐280 [189] . It comprises 18 genes, nine of which with enigmatic function in chetomin production.…”

Section: Epipolythiodioxopiperazines: Bridging the Ringmentioning

confidence: 99%

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Epipolythiodioxopiperazine‐Based Natural Products: Building Blocks, Biosynthesis and Biological Activities

Huber

2022

ChemBioChem

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Activation of secondary metabolite gene clusters in Chaetomium olivaceum via the deletion of a histone deacetylase

Zhao,

Cao,

Wang

et al. 2024

Appl Microbiol Biotechnol

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Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1–A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1–A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. Key points • Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. • Three polyketides and one asterriquinone were isolated from HDAC deleted strain. • Two different PKSs were reported in C. olivaceum SD-80A.

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Proteomic dissection of the role of GliZ in gliotoxin biosynthesis in Aspergillus fumigatus

Traynor¹,

Sarikaya-Bayram²,

Bayram³

et al. 2023

Fungal Genetics and Biology

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Investigation of chetomin as a lead compound and its biosynthetic pathway

Cited by 4 publications

References 35 publications

Epipolythiodioxopiperazine‐Based Natural Products: Building Blocks, Biosynthesis and Biological Activities

Epipolythiodioxopiperazine‐Based Natural Products: Building Blocks, Biosynthesis and Biological Activities

Activation of secondary metabolite gene clusters in Chaetomium olivaceum via the deletion of a histone deacetylase

Proteomic dissection of the role of GliZ in gliotoxin biosynthesis in Aspergillus fumigatus

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