Natural products from plants have served mankind in a wide range of applications, such as medicines, perfumes, or flavoring agents. For this reason, synthesis, regulation and function of plant-derived chemicals, as well as the evolution of metabolic diversity, has attracted researchers all around the world. In particular, vascular plants have been subject to such analyses due to prevalent characteristics such as appearance, fragrance, and ecological settings. In contrast, bryophytes, constituting the second largest group of plants in terms of species number, have been mostly overlooked in this regard, potentially due to their seemingly tiny, simple and obscure nature. However, the identification of highly interesting chemicals from bryophytes with potential for biotechnological exploitation is changing this perception. Bryophytes offer a high degree of biochemical complexity, as a consequence of their ecological and genetic diversification, which enable them to prosper in various, often very harsh habitats. The number of bioactive compounds isolated from bryophytes is growing rapidly. The rapidly increasing wealth of bryophyte genetics opens doors to functional and comparative genomics approaches, including disentangling of the biosynthesis of potentially interesting chemicals, mining for novel gene families and tracing the evolutionary history of metabolic pathways. Throughout the last decades, the moss Physcomitrella (Physcomitrium patens) has moved from being a model plant together with Marchantia polymorpha in fundamental biology into an attractive host for the production of biotechnologically relevant compounds such as biopharmaceuticals. In the future, bryophytes like the moss P. patens might also be attractive candidates for the production of novel bryophyte-derived chemicals of commercial interest. This review provides a comprehensive overview of natural product research in bryophytes from different perspectives together with biotechnological advances throughout the last decade.

Bryophytes (mosses, liverworts and hornworts) often produce high amounts of very long-chain polyunsaturated fatty acids (vl-PUFAs) including arachidonic acid (AA, 20:4 Δ5,8,11,14) and eicosapentaenoic acid (EPA, 20:5 Δ5,8,11,14,17). The presence of vl-PUFAs is common for marine organisms such as algae, but rarely found in higher plants. This could indicate that bryophytes did not lose their marine origin completely when they landed into the non-aqueous environment. Vl-PUFA, especially the omega-3 fatty acid EPA, is essential in human diet for its benefits on healthy brain development and inflammation modulation. Recent studies are committed to finding new sources of vl-PUFAs instead of fish and algae oil. In this review, we summarize the fatty acid compositions and contents in the previous studies, as well as the approaches for qualification and quantification. We also conclude different approaches to enhance AA and EPA productions including biotic and abiotic stresses.

Bryophytes (mosses, liverworts, and hornworts) have interested researchers because of their high chemical diversity and their potential uses in pharmaceutical, food, and cosmetic industries. Specifically, long-chain polyunsaturated fatty acids (l-PUFA) such as arachidonic acid (AA) and eicosapentaenoic acid (EPA) are commonly found in bryophytes, but not in vascular plants. Bryophytes accumulate PUFAs in cold or even freezing temperature to keep the cell fluidity. Iceland has a long history of bryophyte vegetation. These bryophytes are highly adapted to the harsh environment in Iceland and therefore are expected to produce high amounts of PUFAs. However, despite the fact that hundreds of mosses and liverworts have been found in Iceland, their lipid profiles largely remain unknown. In this study, we performed untargeted lipidomics by using UPLC-ESI-QTOF-MS as a rapid screening strategy to examine the lipid compositions of 39 local bryophyte species in Iceland and aimed to find high AA and EPA producers. A total of 280 lipid molecular species from 15 lipid classes were quantified with isotope-labeled internal standards. AA and EPA were abundantly distributed in the phospholipids (mainly PC and PE) and glycerolipids (MGDG and DGDG) in six moss species, namely Racomotrium lanuginosum, R. ericoides, Bryum psedotriquetrium, Plagiomnium ellipticum, Hylocomium splendens, and Rhytidiadelphus triquetrus. Two of the six species (B. psedotriquetrium and H. splendens) also accumulated high concentrations of PUFA-containing-triacylglycerols.

Isoprenoids comprise the largest group of plant specialized metabolites. 1‐deoxy‐D‐xylulose‐5‐phosphate synthase (DXS) is one of the major rate‐limiting enzymes in their biosynthesis. The DXS family expanded structurally and functionally during evolution and is believed to have significantly contributed to metabolic complexity and diversity in plants. This family has not yet been studied in Physcomitrium patens or other bryophytes. Here, we assessed the degree of evolutionary expansion in the DXS family in bryophytes and, more specifically, in P. patens using phylogenetic analysis. Transcriptome profiling was applied to investigate tissue‐specific, developmental, and environmental responses, such as salt stress, in the DXS family. Moreover, the effect of salt stress on terpenoid biosynthesis was monitored through metabolomics. The phylogenetic analysis of DXS revealed that a structural expansion occurred in bryophytes, but not in P. patens. Functional complementation assay revealed functional activity in all four copies. Comparative transcriptomics showed tissue‐ and condition‐specific divergence in the expression profiles of DXS copies and demonstrated specific stress responses for PpDXS1D, particularly to salt stress. These findings coincide with increased flux in the pathway towards downstream metabolites under salt stress. Additionally, co‐expression network analysis revealed significant differences between the co‐expressed genes of the DXS copies and illustrated enrichment of stress‐responsive genes in the PpDXS1D network. These results suggest that the DXS family in P. patens is conserved but undergoes differential transcriptional regulation, which might allow P. patens to fine‐tune DXS levels under different conditions, such as abiotic stress.