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.

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.

Ginsenosides, the predominant bioactive components of Panax species, are biosynthesized by glycosylation at C3–OH and/or C20–OH of protopanaxadiol (PPD), and C6–OH and/or C20–OH of protopanaxatriol (PPT). Dammarenediol-II (DM), the direct precursor of PPD, has two hydroxyls at C3 and C20 positions, but DM glucosides have scarcely been identified from Panax species. Herein, we used two crude recombinant UDP-glycosyltransferases (UGTs), PgUGT74AE2 and UGTPg1 from Panax ginseng, to catalyze the glycosylation of DM with UDP-glucose (UDPG) as the sugar donor to produce DM glucosides 3-O-β-D-glucopyranosyl-dammar-24-ene-3β,20S-diol (3β-O-Glc-DM) and 20-O-β-D-glucopyranosyl-dammar-24-ene-3β,20S-diol (20S-O-Glc-DM), respectively. The in vitro and in vivo assays demonstrated that both 3β-O-Glc-DM and 20S-O-Glc-DM exhibited higher anti-colon cancer activities than natural ginsenosides. In order to produce DM glucosides in an economical, efficient and convenient way, we refactored the complete biosynthetic pathways of 3β-O-Glc-DM and 20S-O-Glc-DM by introducing the codon-optimized genes encoding DM synthase (DS) together with PgUGT74AE2 or UGTPg1 into Saccharomyces cerevisiae, respectively. Furthermore, multistep metabolic engineering strategies were applied, including optimization of chassis cell, multi-copy integration of heterologous genes via the CRISPR/Cas9 system, increase of precursor supply by overexpressing rate-limiting enzymes, down-regulation of the competitive pathway to redirect the metabolic flux towards the target products, and overexpression of the transcriptional activator. Finally, the titers of 2.4 g L⁻¹ 3β-O-Glc-DM and 5.6 g L⁻¹ 20S-O-Glc-DM were achieved through fed-batch fermentation in a 3 L bioreactor. This is the first study to demonstrate the anti-colon cancer activities of DM glucosides and to achieve the de novo biosynthesis of DM glucosides with high titers in microbial cell factories. This study has established a green and sustainable approach for the industrial production of DM glucosides, which provides promising candidates for new drug research and development.

Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey’s method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC₅₀ value of 0.414 μM.

By treating with histone-deacetylase inhibitor valproate sodium, three new heterdimeric tetrahydroxanthone–chromanone lactones chrysoxanthones A–C (1–3), along with 17 known compounds were isolated from a sponge-associated Penicillium chrysogenum HLS111. The planar structures of chrysoxanthones A–C were elucidated by means of spectroscopic analyses, including MS, 1D, and 2D NMR. Their absolute configurations were established by electronic circular dichroism (ECD) calculations. Chrysoxanthones A–C exhibited moderate antibacterial activities against Bacillus subtilis with minimum inhibitory concentration (MIC) values of 5–10 μg/mL.

Background: Rhododendron molle(Ericaceae) is a traditional Chinese medicine, which has been used to treat rheumatism and relieve pain since ancient times. The characteristic grayanoids of this plant have been demonstrated to be the chemical basis for the analgesic activity. Moreover, unlike morphine, these diterpenoids are non-addictive. Grayanoids mainly distribute in the leaves, flowers, roots, and fruits ofR. molle, with low content. Currently the research on the biosynthesis of grayanoids is hindered, partially due to lack of the genomic information.Results: In the present study, a total of 744 Mb sequences were generated and assembled into 13 chromosomes. An ancient whole-genome duplication event (Ad-β) was discovered that occurred around 70 million years ago. Tandem and segmental gene duplications led to specific gene expansions in the terpene synthase and cytochrome P450 (CYP450) gene families. Two diterpene synthases were demonstrated to be responsible for the biosynthesis of 16α-hydroxy-ent-kaurane, the key precursor for grayanoids. Phylogenetic analysis revealed a species-specific bloom of the CYP71AU subfamily, which may involve the candidate CYP450s responsible for the biosynthesis of grayanoids. Additionally, three putative terpene biosynthetic gene clusters were found.Conclusions: We reported the first genome assembly ofR. molleand investigated the molecular basis underpinning terpenoids biosynthesis. Our work provides a foundation for elucidating the complete biosynthetic pathway of grayanoids and studying the terpenoids diversity inR. molle.