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Medicinal plants have been used by mankind since ancient times, and many bioactive plant secondary metabolites are applied nowadays both directly as drugs, and as raw materials for semi-synthetic modifications. However, the structural complexity often thwarts cost-efficient chemical synthesis, and the usually low content in the native plant necessitates the processing of large amounts of field-cultivated raw material. The biotechnological manufacturing of such compounds offers a number of advantages like predictable, stable, and year-round sustainable production, scalability, and easier extraction and purification. Plant cell and tissue culture represents one possible alternative to the extraction of phytochemicals from plant material. Although a broad commercialization of such processes has not yet occurred, ongoing research indicates that plant in vitro systems such as cell suspension cultures, organ cultures, and transgenic hairy roots hold a promising potential as sources for bioactive compounds. Progress in the areas of biosynthetic pathway elucidation and genetic manipulation has expanded the possibilities to utilize plant metabolic engineering and heterologous production in microorganisms. This review aims to summarize recent advances in the in vitro production of high-value plant secondary metabolites of medicinal importance.Key points• Bioactive plant secondary metabolites are important for current and future use in medicine• In vitro production is a sustainable alternative to extraction from plants or costly chemical synthesis• Current research addresses plant cell and tissue culture, metabolic engineering, and heterologous production

The rise in global temperature also favors the multiplication of pests and pathogens, which calls into question global food security. Plants have developed special coping mechanisms since they are sessile and lack an immune system. These mechanisms use a variety of secondary metabolites as weapons to avoid obstacles, adapt to their changing environment, and survive in less-than-ideal circumstances. Plant secondary metabolites include phenolic compounds, alkaloids, glycosides, and terpenoids, which are stored in specialized structures such as latex, trichomes, resin ducts, etc. Secondary metabolites help the plants to be safe from biotic stressors, either by repelling them or attracting their enemies, or exerting toxic effects on them. Modern omics technologies enable the elucidation of the structural and functional properties of these metabolites along with their biosynthesis. A better understanding of the enzymatic regulations and molecular mechanisms aids in the exploitation of secondary metabolites in modern pest management approaches such as biopesticides and integrated pest management. The current review provides an overview of the major plant secondary metabolites that play significant roles in enhancing biotic stress tolerance. It examines their involvement in both indirect and direct defense mechanisms, as well as their storage within plant tissues. Additionally, this review explores the importance of metabolomics approaches in elucidating the significance of secondary metabolites in biotic stress tolerance. The application of metabolic engineering in breeding for biotic stress resistance is discussed, along with the exploitation of secondary metabolites for sustainable pest management.

Many types of research have distinctly addressed the efficacy of natural plant metabolites used for human consumption both in cell culture and preclinical animal model systems. However, these in vitro and in vivo effects have not been able to be translated for clinical use because of several factors such as inefficient systemic delivery and bioavailability of promising agents that significantly contribute to this disconnection. Over the past decades, extraordinary advances have been made successfully on the development of novel drug delivery systems for encapsulation of plant active metabolites including organic, inorganic and hybrid nanoparticles. The advanced formulas are confirmed to have extraordinary benefits over conventional and previously used systems in the manner of solubility, bioavailability, toxicity, pharmacological activity, stability, distribution, sustained delivery, and both physical and chemical degradation. The current review highlights the development of novel nanocarrier for plant active compounds, their method of preparation, type of active ingredients, and their biomedical applications.

Both hormones are important for plant growth and development, and response to biotic and abiotic stress stimuli (Al-Babili and Bouwmeester, 2015;Wang et al., 2021). [...]SLs are some of the best-known examples of underground signaling molecules in plant-microbe and plant-plant communication (Lanfranco et al., 2018). Research in this field has been aggravated by the very low quantities of root-secreted specialized metabolites, which hinders their identification, structural characterizations, and detailed assessment of their biological function. [...]researchers need to collect root exudates at large scale to get insights into their metabolite compositions (Ueno et al., 2021). [...]our research collection also provides important perspectives on the overlooked regulatory and signaling metabolites in the rhizosphere, paving the way for future investigations.

Flavonoids and other phenolic constituents are a large group of plant metabolites that have long attracted interest from researchers worldwide due to their functions in plant physiology, as well as their huge number of benefits for human health and well-being. This review attempts to reveal a promising view of the major physiological roles of flavonoids and other phenolic phytochemical molecules, e.g., protection agents against UV damage, pathogen defense agents, detoxifying agents, and agents promoting pollen fertility and successful pollination. Besides, the value of both flavonoids and other phenolic phytochemicals for plant species delimitation was also emphasized for the first time with the determination of their major physiological roles. Furthermore, their medical benefits for mankind were also highlighted in this current work.

With the widespread use of antibiotic drugs worldwide and the global increase in the number of immunodeficient patients, fungal infections have become a serious threat to global public health security. Moreover, the evolution of fungal resistance to existing antifungal drugs is on the rise. To address these issues, the development of new antifungal drugs or fungal inhibitors needs to be targeted urgently. Plant secondary metabolites are characterized by a wide variety of chemical structures, low price, high availability, high antimicrobial activity, and few side effects. Therefore, plant secondary metabolites may be important resources for the identification and development of novel antifungal drugs. However, there are few studies to summarize those contents. In this review, the antifungal modes of action of plant secondary metabolites toward different types of fungi and fungal infections are covered, as well as highlighting immunomodulatory effects on the human body. This review of the literature should lay the foundation for research into new antifungal drugs and the discovery of new targets.Key points• Immunocompromised patients who are infected the drug-resistant fungi are increasing.• Plant secondary metabolites toward various fungal targets are covered.• Plant secondary metabolites with immunomodulatory effect are verified in vivo.

Background Plant specialized (or secondary) metabolites (PSM), also known as phytochemicals, natural products, or plant constituents, play essential roles in interactions between plants and environment. Although many research efforts have focused on discovering novel metabolites and their biosynthetic genes, the resolution of metabolic pathways and identified biosynthetic genes was limited by rudimentary analysis approaches and enormous number of candidate genes. Results Here we integrated state-of-the-art automated machine learning (ML) frame AutoGluon-Tabular and multi-omics data from Arabidopsis to predict genes encoding enzymes involved in biosynthesis of plant specialized metabolite (PSM), focusing on the three main PSM categories: terpenoids, alkaloids, and phenolics. We found that the related features of genomics and proteomics were the top two crucial categories of features contributing to the model performance. Using only these key features, we built a new model in Arabidopsis , which performed better than models built with more features including those related with transcriptomics and epigenomics. Finally, the built models were validated in maize and tomato, and models tested for maize and trained with data from two other species exhibited either equivalent or superior performance to intraspecies predictions. Conclusions Our external validation results in grape and poppy on the one hand implied the applicability of our model to the other species, and on the other hand showed enormous potential to improve the prediction of enzymes synthesizing PSM with the inclusion of valid data from a wider range of species.

Infectious diseases that are caused by bacteria are an important cause of mortality and morbidity in all regions of the world. Bacterial drug resistance has grown in the last decades, but the rate of discovery of new antibiotics has steadily decreased. Therefore, the search for new effective antibacterial agents has become a top priority. The plant kingdom seems to be a deep well for searching for novel antimicrobial agents. This is due to the many attractive features of plants: they are readily available and cheap, extracts or compounds from plant sources often demonstrate high-level activity against pathogens, and they rarely have severe side effects. The huge variety of plant-derived compounds provides very diverse chemical structures that may supply both the novel mechanisms of antimicrobial action and provide us with new targets within the bacterial cell. In addition, the rapid development of modern biotechnologies opens up the way for obtaining bioactive compounds in environmentally friendly and low-toxic conditions. In this short review, we ask the question: do antibacterial agents derived from plants have a chance to become a panacea against infectious diseases in the “post-antibiotics era”.

Diverse secondary metabolites in plants, with their rich biological activities, have long been important sources for human medicine, food additives, pesticides, etc. However, the large-scale cultivation of host plants consumes land resources and is susceptible to pest and disease problems. Additionally, the multi-step and demanding nature of chemical synthesis adds to production costs, limiting their widespread application. In vitro cultivation and the metabolic engineering of plants have significantly enhanced the synthesis of secondary metabolites with successful industrial production cases. As synthetic biology advances, more research is focusing on heterologous synthesis using microorganisms. This review provides a comprehensive comparison between these two chassis, evaluating their performance in the synthesis of various types of secondary metabolites from the perspectives of yield and strategies. It also discusses the challenges they face and offers insights into future efforts and directions.

Many plants produce secondary metabolites (PSMs) with antiviral activities. Among the antiviral PSMs, lipophilic terpenoids in essential oils can disturb the lipid envelope of viruses. Phenols and polyphenols (flavonoids, rosmarinic acid and tannins) attack viral proteins present in the viral membrane or inside the virus particle. Both phenolics and essential oils are active against free viral particles but not—or to a lesser degree—after a virus has entered a host cell. Another group of PSMs is directed against DNA or RNA. These are DNA intercalators such as sanguinarine, berberine, emetine and other isoquinoline alkaloids, ß-carboline, and quinoline alkaloids such as quinine, cinchonine, dictamine and skimmianine. The DNA intercalators stabilize double-stranded nucleic acids and inhibit the replication, transcription, and translation of genetic material. These alkaloids can inhibit viral development and viral replication in cells, as shown for SARS-CoV-1 and other viruses. Since chloroquine (which is also a DNA intercalator and a chemical derivative of the alkaloid quinine) is apparently clinically helpful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, it is assumed that intercalating alkaloids, or the medicinal plants producing them, may be interesting candidates for the development of new antiviral drugs for the treatment of coronavirus disease 2019 (COVID-19).