Cordyceps militaris, also called as bei-chong-cao, is an insect-pathogenic fungus from the Ascomycota phylum and the Clavicipitaceae family. It is a valuable filamentous fungus with medicinal and edible properties that has been utilized in traditional Chinese medicine (TCM) and as a nutritious food. Cordycepin is the bioactive compound firstly isolated from C. militaris and has a variety of nutraceutical and health-promoting properties, making it widely employed in nutraceutical and pharmaceutical fields. Due to the low composition and paucity of wild resources, its availability from natural sources is limited. With the elucidation of the cordycepin biosynthetic pathway and the advent of synthetic biology, a green cordycepin biosynthesis in Saccharomyces cerevisiae and Metarhizium robertsii has been developed, indicating a potential sustainable production method of cordycepin. Given that, this review primarily focused on the metabolic engineering and heterologous biosynthesis strategies of cordycepin.

Ophiocordyceps sinensis (Berk.) is an entomopathogenic fungus that can infect the larva of the ghost moth, Hepialus xiaojinensis, causing mummification after more than one year. This prolonged infection provides a valuable model for studying the immunological interplay between an insect host and a pathogenic fungus. A comparative transcriptome analysis of pre-infection (L) and one-year post-infection (IL) larvae was performed to investigate the immune response in the host. Here, a total of 59,668 unigenes were obtained using Illumina Sequencing in IL and L. Among the 345 identified immune-related genes, 83 out of 86 immune-related differentially expressed genes (DEGs) had a much higher expression in IL than in L. Furthermore, the immune-related DEGs were classified as pathogen recognition receptors (PRRs), signal modulators or transductors, and immune effector molecules. Serpins and protease inhibitors were found to be upregulated in the late phase of infection, suppressing the host’s immune response. Based on the above analysis, the expression levels of most immune-related genes would return to the baseline with the immune response being repressed in the late phase of infection, leading to the fungal immunological tolerance after prolonged infection. Meanwhile, the transcriptomes of IL and the mummified larva (ML) were compared to explore O. sinensis invasion. A total of 1408 novel genes were identified, with 162 of them annotated with putative functions. The gene families likely implicated in O. sinensis pathogenicity have been identified, primarily including serine carboxypeptidase, peroxidase, metalloprotease peptidase, aminopeptidases, cytochrome P450, and oxidoreductase. Furthermore, quantitative real-time PCR (qPCR) was used to assess the expression levels of some critical genes that were involved in immune response and fungal pathogenicity. The results showed that their expression levels were consistent with the transcriptomes. Taken together, our findings offered a comprehensive and precise transcriptome study to understand the immune defense in H. xiaojinensis and O. sinensis invasion, which would accelerate the large-scale artificial cultivation of this medicinal fungus.

Posttranslational modifications play pivotal roles in the regulation of protein function, enabling precise and dynamic control of diverse cellular processes in fungi. Classical and emerging PTMs, such as phosphorylation, ubiquitination, acetylation, lysine succinylation, and SUMOylation, glycosylation, lipidation modifications, S-acylation, or S-palmitoylation, critically modulate the activity and behavior of proteins. In recent years, research efforts have increasingly focused on global PTMs profiling and functional characterization across fungal species. PTMs function in multiple cellular processes, such as meiosis, cell wall integrity, autophagy, reactive oxygen species metabolism, RNA editing, finely regulating the fungal sexual development and virulence. More recently, the biomolecular condensates dynamics resembled by PTMs modulate host–pathogen interactions. Furthermore, the crosstalk between different PTMs on a single protein and interacting proteins allows for sophisticated regulatory control over fungal development, adaptation, and pathogenicity. However, the full scope of PTMs in the fungal sexual development and pathogenesis in plant remains to be fully elucidated. This review offers a comprehensive analysis of the roles of PTMs in sexual development of the model and plant pathogenic filamentous fungi. It offers mechanistic insights into how the PTMs regulate biological processes, cellular functions and integrate environmental cues, ultimately modulating sexual progression and virulence. A deeper understanding of the roles and regulatory mechanisms of PTMs will facilitate the development of effective strategies for industrially valuable fungi breeding and plant diseases control.