To date, little is known about the evolution of fern genomes, with only two small genomes published from the heterosporous Salviniales. Here we assembled the genome of Alsophila spinulosa, known as the flying spider-monkey tree fern, onto 69 pseudochromosomes. The remarkable preservation of synteny, despite resulting from an ancient whole-genome duplication over 100 million years ago, is unprecedented in plants and probably speaks to the uniqueness of tree ferns. Our detailed investigations into stem anatomy and lignin biosynthesis shed new light on the evolution of stem formation in tree ferns. We identified a phenolic compound, alsophilin, that is abundant in xylem, and we provided the molecular basis for its biosynthesis. Finally, analysis of demographic history revealed two genetic bottlenecks, resulting in rapid demographic declines of A. spinulosa. The A. spinulosa genome fills a crucial gap in the plant genomic landscape and helps elucidate many unique aspects of tree fern biology.

The protection and sustainable utilization of natural resources are among the most pressing global problems of the 21st century. Taxol is a well-known anticancer agent with a unique active mechanism, mainly isolated from the slow-growing yew tree, which has achieved the status of “blockbuster drug” due to its popularity in the treatment of cancers. However, the source of Taxol has always been a primary concern, because its content in the plant is extremely low. In this review, we introduce the advances in exploring alternative Taxol sources aside from total synthesis, including Taxol from nursery cultivated Taxus, semi-synthesis of Taxol, Taxol from Taxus cell culture, production of Taxol by synthetic biology, Taxol from the endophytic fungi and Taxol from other non-Taxus plants. The future perspective of Taxol production is also discussed.

As the main bioactive constituents of Panax species, ginsenosides possess a wide range of notable medicinal effects such as anti-cancer, anti-oxidative, antiaging, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, the increasing medical demand for ginsenosides cannot be met due to the limited resource of Panax species and the low contents of ginsenosides. In recent years, biotechnological approaches have been utilized to increase the production of ginsenosides by regulating the key enzymes of ginsenoside biosynthesis, while synthetic biology strategies have been adopted to produce ginsenosides by introducing these genes into yeast. This review summarizes the latest research progress on cloning and functional characterization of key genes dedicated to the production of ginsenosides, which not only lays the foundation for their application in plant engineering, but also provides the building blocks for the production of ginsenosides by synthetic biology.

Cordycepin is a bioactive component of the fungus Cordyceps militaris. Previously, we showed that cordycepin can alleviate hyperlipidemia through enhancing the phosphorylation of AMP‐activated protein kinase (AMPK), but the mechanism of this stimulation is unknown. Here, we investigated the potential mechanisms of cordycepin‐induced AMPK activation in HepG2 cells. Treatment with cordycepin largely reduced oleic acid (OA)‐elicited intracellular lipid accumulation and increased AMPK activity in a dose‐dependent manner. Cordycepin‐induced AMPK activation was not accompanied by changes in either the intracellular levels of AMP or the AMP/ATP ratio, nor was it influenced by calmodulin‐dependent protein kinase kinase (CaMKK) inhibition; however, this activation was significantly suppressed by liver kinase B1 (LKB1) knockdown. Molecular docking, fluorescent and circular dichroism measurements showed that cordycepin interacted with the γ1 subunit of AMPK. Knockdown of AMPKγ1 by siRNA substantially abolished the effects of cordycepin on AMPK activation and lipid regulation. The modulating effects of cordycepin on the mRNA levels of key lipid regulatory genes were also largely reversed when AMPKγ1 expression was inhibited. Together, these data suggest that cordycepin may inhibit intracellular lipid accumulation through activation of AMPK via interaction with the γ1 subunit.

The diversity and biological activities of fungi associated with the two sponges, Haliclona simulans and Gelliodes carnosa, were investigated using a culture-dependent method followed by analysis of the fungal rDNA-ITS sequences. The two sponges were collected from the coastal waters of Lingshui Bay of Hainan Island in the South China Sea. A total of 37 independent fungal isolates corresponding to 30 different species were obtained from the two sponges. Nearly two thirds of the strains (n = 24, 64.9%) had close affiliations (identity (ID) or similarity ≥ 98%) with their best matches in GenBank. Another one third of the isolates (n = 13, 35.1%) were distantly related to their closest relatives (ID < 98%), implying that these species are possibly different from those previously reported. The two sponges possessed similar fungal diversities. Haliclona simulans harbored a mainly different fungal consortium as compared with that of the same sponge species collected from Irish coastal waters, suggesting that the fungal diversity associated with the sponges is more dependent on the surrounding environment than on the sponge species. Biological activities of the fungal culture extracts were tested against the human tumor cell lines, mainly, a human lung carcinoma cell line (A-549), a human liver carcinoma cell line (Bel-7402), and a human colon carcinoma cell line (HCT-8), and against the Gram positive bacterium Bacillus subtilis. A relatively high proportion of positive results were obtained in this study, demonstrating that fungi isolated from sponges could be a rich source of new biologically active natural products.

Scaling-up of high-cell-density fermentation (HCDF) of Pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final technological hurdle in the decision to go commercial. However, related investigations have rarely been reported. In this paper, we study the scaling-up processes of a recombinant P. pastoris from the pilot (10 to 100-L) to the demonstration (1,000-L) scales, which can be used to convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol by the β-xylosidase for semi-synthesis of Taxol. We demonstrated that a pure oxygen supplement can be omitted from the HCDF if the super atmospheric pressure was increased from 0.05 to 0.10 ± 0.05 MPa and we developed a new methanol feeding biomass-stat strategy (0.035 mL/g/h) with 1% dissolved oxygen and 100 g/L initial induction biomass (dry cell weight). The scaling-up was reproducible and the best results were obtained from the 1,000-L scale, featuring a shorter induction time and the highest enzyme activities and productions, respectively. The specific growth and specific production rates were also determined. This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through the recombinant yeast. It also provides a successful paradigm for scaling-up HCDF of P. pastoris to the demonstration scale.