The evolution of chemodiversity in plants-From verbal to quantitative models.

Plants harbour a great chemodiversity, that is diversity of specialised metabolites (SMs), at different scales. For instance, individuals can produce a large number of SMs, and populations can differ in their metabolite composition. Given the ecological and economic importance of plant chemodiversity, it is important to understand how it arises and is maintained over evolutionary time. For other dimensions of biodiversity, that is species diversity and genetic diversity, quantitative models play an important role in addressing such questions. Here, we provide a synthesis of existing hypotheses and quantitative models, that is mathematical models and computer simulations, for the evolution of plant chemodiversity. We describe each model's ingredients, that is the biological processes that shape chemodiversity, the scales it considers and whether it has been formalized as a quantitative model. Although we identify several quantitative models, not all are dynamic and many influential models have remained verbal. To fill these gaps, we outline our vision for the future of chemodiversity modelling. We identify quantitative models used for genetic variation that may be adapted for chemodiversity, and we present a flexible framework for the creation of individual-based models that address different scales of chemodiversity and combine different ingredients that bring this chemodiversity about.

Molecular-level insight into the effect of fertilization regimes on the chemodiversity of dissolved organic matter in tropical cropland.

Fertilization is a critical agronomic measure for croplands in tropical regions, owing to their low fertility. However, the effects of fertilization on the quantity and chemodiversity of latosolic dissolved organic matter (DOM) in tropical regions remain largely unknown. Therefore, in this study, the variations in latosol DOM concentrations and chemodiversity induced by inorganic fertilization and the co-application of inorganic fertilization with straw return, sheep manure, biochar, and vermicompost fertilizers at a molecular level were systematically investigated using multispectral techniques and ultrahigh-resolution mass spectrometry. In line with our expectations, the results showed that combined inorganic-organic fertilization improved soil quality by increasing soil organic carbon content compared to that under inorganic fertilization. However, as the most active and bioavailable organic carbon pool, dissolved organic carbonconcentrations between the fertilization treatments were not significantly different (p = 0.07). However, the dissolved organic carbon concentrations under combined inorganic-organic fertilization treatment (NPK plus straw return, 263.45 ± 37.51 mg/kg) were lower than those under inorganic fertilization treatment (282.10 ± 18.57 mg/kg). Spectral analysis showed that the DOM in the combined inorganic-organic fertilization treatments had a higher degree of humification and lower autogenetic contributions. Furthermore, Fourier transform ion cyclotron resonance mass spectrometry analysis indicated that the combined inorganic-organic fertilization increased the chemodiversity of latosolic DOM and promoted the production of large, oxidized, and stable molecules, including lignin, aromatic, and tannin compounds, which potentially benefits soil carbon sequestration in tropical regions. This study could provide a theoretical basis for elucidating on the potentially relevant ecological functions and environmental effects of DOM under fertilization regimes.

Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria.

Cyanobacteria are rich producers of secondary metabolites, excreting some of these to the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains were characterized by HR-ESI-LC-MS/MS. Cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116, while the reduction in lipids was tested in zebrafish larvae and in a steatosis model with fatty acid-overloaded human liver cells. The exometabolome analysis using GNPS revealed many complex clusters of unique compounds in several strains, with no identifications in public databases. Three strains reduced viability in HCT116 cells, namely Tolypotrichaceae BACA0428 (30.45%), Aphanizomenonaceae BACA0025 (40.84%), and Microchaetaceae BACA0110 (46.61%). Lipid reduction in zebrafish larvae was only observed by exposure to Dulcicalothrix sp. BACA0344 (60%). The feature-based molecular network shows that this bioactivity was highly correlated with two flavanones, a compound class described in the literature to have lipid reduction activity. The exometabolome characterization of cyanobacteria strains revealed a high chemodiversity, which supports it as a source for novel bioactive compounds, despite most of the time being overlooked.

Characteristics of dissolved organic matter (DOM) in Chinese farmland soils under different climate zone types: A molecular perspective.

Interactions between dissolved organic matter (DOM) and surrounding environments are highly complex. Understanding DOM at the molecular level can contribute to the management of soil pollution and safeguarding agricultural fields. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) has enabled a molecular-level understanding of DOM. Accordingly, in this study, we investigated soil samples from 27 different regions of mainland China with various soil types and climatic characteristics. Based on the geographical features of the four typical climatic zones in mainland China (temperate monsoon, temperate continental, subtropical monsoon, and Qinghai-Tibet Plateau climates), we employed high-resolution mass spectrometry to determine the molecular diversity of DOM under different climatic conditions. The results indicated that lignin and tannin-like substances were the most active categories of DOM in the soils. Collectively, the composition and unsaturation of DOM molecules are influenced by sunlight, precipitation, temperature, and human activity. All climatic regions contained a substantial number of characteristic molecules, with CHO and CHON constituting over 80%, and DOM containing nitrogen and sulfur was relatively more abundant in the monsoon regions. The complex composition of DOM incorporates various active functional groups, such as -NO2 and -ONO2. Furthermore, soil DOM in the monsoon regions showed higher unsaturation and facilitated various (bio) biochemical reactions in the soil.

Steroidal glycoside profile differences among primary roots system and adventitious roots in Solanum dulcamara.

MAIN CONCLUSION: Solanum dulcamara primary and adventitious roots showed qualitative and quantitative differences in their steroidal glycosides profile. This opened new venues to evaluate the bioactivity of these molecules in belowground ecosystems. The Solanum genus is characterized by the presence of steroidal glycosides (SGs) that confer herbivore resistance and serve as drug precursors in the pharmaceutical industry. Solanum dulcamara is a self-compatible, sexually reproducing species that produces seeds after buzz-pollination. In addition, primordia on the stem facilitate clonal propagation via adventitious root (AR) formation. ARs contain aerenchyma being developmentally and morphologically different from primary roots (PRs). Therefore, we hypothesized that ARs and PRs have different SG profiles. Aiming to assess differences in SGs profiles in S. dulcamara roots in relation to their origins and morphologies, we used liquid chromatography coupled to electron spray ionization quadruple time of flight mass spectrometry (LC-ESI-qToF-MS) to profile SGs from PRs and ARs of seven S. dulcamara individuals. Mass fragmentation pattern analysis indicated the presence of 31 SG-type structures, including those with spirostans and furostans moieties. We assigned the 31 structures to 9 classes of steroidal aglycons (SAgls) that differ in hydroxylation and degree of unsaturation. We found that SAgls were conjugated with di-, tri- and tetra saccharides whereby one compound contained a malonylated sugar. Principle component analysis showed that SG profiles of PRs and ARs separated on the first principal component, supporting our hypothesis. Specifically, PRs contain higher number of SGs than ARs with some compounds exclusively present in PRs. Our results reveal a high level of novel chemodiversity in PRs and ARs of Solanum dulcamara. The knowledge gained will deepen our understanding of SGs biosynthesis and their functional role in plant-environment interactions.

Quantifying chemodiversity considering biochemical and structural properties of compounds with the R package chemodiv.

Plants produce large numbers of phytochemical compounds affecting plant physiology and interactions with their biotic and abiotic environment. Recently, chemodiversity has attracted considerable attention as an ecologically and evolutionary meaningful way to characterize the phenotype of a mixture of phytochemical compounds. Currently used measures of phytochemical diversity, and related measures of phytochemical dissimilarity, generally do not take structural or biosynthetic properties of compounds into account. Such properties can be indicative of the compounds' function and inform about their biosynthetic (in)dependence, and should therefore be included in calculations of these measures. We introduce the R package chemodiv, which retrieves biochemical and structural properties of compounds from databases and provides functions for calculating and visualizing chemical diversity and dissimilarity for phytochemicals and other types of compounds. Our package enables calculations of diversity that takes the richness, relative abundance and - most importantly - structural and/or biosynthetic dissimilarity of compounds into account. We illustrate the use of the package with examples on simulated and real datasets. By providing the R package chemodiv for quantifying multiple aspects of chemodiversity, we hope to facilitate investigations of how chemodiversity varies across levels of biological organization, and its importance for the ecology and evolution of plants and other organisms.

Soil organic matter dynamics mediated by arbuscular mycorrhizal fungi - an updated conceptual framework.

Arbuscular mycorrhizal (AM) fungi play an important role in soil organic matter (SOM) formation and stabilization. Previous studies have emphasized organic compounds produced by AM fungi as persistent binding agents for aggregate formation and SOM storage. This concept overlooks the multiple biogeochemical processes mediated by AM fungal activities, which drive SOM generation, reprocessing, reorganization, and stabilization. Here, we propose an updated conceptual framework to facilitate a mechanistic understanding of the role of AM fungi in SOM dynamics. In this framework, four pathways for AM fungi-mediated SOM dynamics are included: 'Generating', AM fungal exudates and biomass serve as key sources of SOM chemodiversity; 'Reprocessing', hyphosphere microorganisms drive SOM decomposition and resynthesis; 'Reorganizing', AM fungi mediate soil physical changes and influence SOM transport, redistribution, transformation, and storage; and 'Stabilizing', AM fungi drive mineral weathering and organo-mineral interactions for SOM stabilization. Moreover, we discuss the AM fungal role in SOM dynamics at different scales, especially when translating results from small scales to complex larger scales. We believe that working with this conceptual framework can allow a better understanding of AM fungal role in SOM dynamics, therefore facilitating the development of mycorrhiza-based technologies toward soil health and global change mitigation.

Population divergence in heat and drought responses of a coastal plant: from metabolic phenotypes to plant morphology and growth.

Studying intraspecific variation in multistress responses is central for predicting and managing the population dynamics of wild plant species under rapid global change. Yet, it remains a challenging goal in this field to integrate knowledge on the complex biochemical underpinnings for the targeted 'non-model' species. Here, we studied divergence in combined drought and heat responses among Northern and Southern European populations of the dune plant Cakile maritima, by combining comprehensive plant phenotyping with metabolic profiling via FT-ICR-MS and UPLC-TQ-MS/MS. We observed pronounced constitutive divergence in growth phenology, leaf functional traits, and defence chemistry (glucosinolates and alkaloids) among population origins. Most importantly, the magnitude of growth reduction under drought was partly weaker in southern plants and associated with divergence in plastic growth responses (leaf abscission) and the modulation of primary and specialized metabolites with known central functions not only in plant abiotic but also in biotic stress responses. Our study indicates that divergent selection has shaped the constitutive and drought-/heat-induced expression of numerous morphological and biochemical functional traits to mediate higher abiotic stress resistance in southern Cakile populations, and highlights that metabolomics can be a powerful tool to explore the underlying mechanisms of local adaptation in 'non-model' species.

Chemodiversity of Dissolved Organic Matter Is Governed by Microbial Biogeography in Inland Waters.

Dissolved organic matter (DOM) is crucial for the carbon biogeochemical cycle and has a close link with microbiome in aquatic ecosystems; however, the causal relationship between DOM and microbial diversity in inland waters is not very clear so far. Therefore, a national survey of China's inland waters was conducted, and the DOM chemical composition and microbial community composition were determined by Fourier transform ion cyclotron resonance mass spectrometry and high-throughput sequencing to clarify the abovementioned question. Here, we found that DOM chemodiversity was governed by microbial community assembly in inland waters, not vice versa. Under the control of microbial biogeography, DOM chemodiversity showed a clear geographical distribution difference. Water DOM chemodiversity was mainly constrained by bacterial and archaeal community composition, whereas sediment DOM chemodiversity was mainly controlled by eukaryotic and fungal community composition. In addition, the sediment DOM chemical composition was also affected by the interaction of different microbial groups between waters and sediments. The study is the first to clarify the causal relationship and proposes a microbial regulatory mechanism on the geographical distribution pattern of DOM chemodiversity, thus further deepening the understanding of the DOM biogeochemical cycle.

Sunlight irradiation promotes both the chemodiversity of terrestrial DOM and the biodiversity of bacterial community in a subalpine lake.

Alpine lake habitats are evolving into subalpine lakes under the scenario of climate change, where the vegetation are promoted due to increasing temperature and precipitation. The abundant terrestrial dissolved organic matter (TDOM) leached from watershed soil into subalpine lakes would undergo strong photochemical reaction due to the high altitude, with the potential to alter DOM composition and affect the bacterial communities. To reveal the transformation of TDOM by both photochemical and microbial processes in a typical subalpine lake, Lake Tiancai (located 200 m below the tree line) was chosen. TDOM was extracted from the surrounding soil of Lake Tiancai and then subjected to the photo/micro-processing for 107 days. The transformation of TDOM was analyzed by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and fluorescence spectroscopy, and the shift of bacterial communities was analyzed using 16s rRNA gene sequencing technology. Dissolved organic carbon and light-absorbing components (a350) decay accounted for approximately 40% and 80% of the original, respectively, in the sunlight process, but both less than 20% in the microbial process for 107 days. The photochemical process promoted the chemodiversity as there were ∼7000 molecules after sunlight irradiation, compared to ∼3000 molecules in the original TDOM. Light promoted the production of highly unsaturated molecules and aliphatics, which were significantly associated with Bacteroidota, suggesting that light may influence bacterial communities by regulating the DOM molecules. Carboxylic-rich alicyclic molecules were generated in both photochemical and biological processes, suggesting TDOM was converted to a stable pool over time. Our finding on the transformation of terrestrial DOM and the alternation of bacterial community under the simultaneously photochemical and microbial processes will help to reveal the response of the carbon cycle and lake system structure to climate change for high-altitude lakes.

Differential Regulation and Production of Secondary Metabolites among Isolates of the Fungal Wheat Pathogen Zymoseptoria tritici.

The genome of the wheat-pathogenic fungus Zymoseptoria tritici represents extensive presence-absence variation in gene content. Here, we addressed variation in biosynthetic gene cluster (BGC) content and biochemical profiles among three isolates. We analyzed secondary metabolite properties based on genome, transcriptome, and metabolome data. The isolates represent highly distinct genome architecture but harbor similar repertoires of BGCs. Expression profiles for most BGCs show comparable patterns of regulation among the isolates, suggesting a conserved biochemical infection program. For all three isolates, we observed a strong upregulation of a putative abscisic acid (ABA) gene cluster during biotrophic host colonization, indicating that Z. tritici interferes with host defenses by the biosynthesis of this phytohormone. Further, during in vitro growth, the isolates show similar metabolomes congruent with the predicted BGC content. We assessed if secondary metabolite production is regulated by histone methylation using a mutant impaired in formation of facultative heterochromatin (H3K27me3). In contrast to other ascomycete fungi, chromatin modifications play a less prominent role in regulation of secondary metabolites. In summary, we show that Z. tritici has a conserved program of secondary metabolite production, contrasting with the immense variation in effector expression, and some of these metabolites might play a key role during host colonization. IMPORTANCE Zymoseptoria tritici is one of the most devastating pathogens of wheat. So far the molecular determinants of virulence and their regulation are poorly understood. Previous studies have focused on proteinaceous virulence factors and their extensive diversity. In this study, we focus on secondary metabolites produced by Z. tritici. Using a comparative framework, we characterize core and noncore metabolites produced by Z. tritici by combining genome, transcriptome, and metabolome data sets. Our findings indicate highly conserved biochemical profiles with contrasting genetic and phenotypic diversity of the field isolates investigated here. This discovery has relevance for future crop protection strategies.

ATP-binding cassette transporters in nonmodel plants.

Knowledge about plant ATP-binding cassette (ABC) proteins is of great value for sustainable agriculture, economic yield, and the generation of high-quality products, especially under unfavorable growth conditions. We have learned much about ABC proteins in model organisms, notably Arabidopsis thaliana; however, the importance of research dedicated to these transporters extends far beyond Arabidopsis biology. Recent progress in genomic and transcriptomic approaches for nonmodel and noncanonical model plants allows us to look at ABC transporters from a wider perspective and consider chemodiversity and functionally driven adaptation as distinctive mechanisms during their evolution. Here, by considering several representatives from agriculturally important families and recent progress in functional characterization of nonArabidopsis ABC proteins, we aim to bring attention to understanding the evolutionary background, distribution among lineages and possible mechanisms underlying the adaptation of this versatile transport system for plant needs. Increasing the knowledge of ABC proteins in nonmodel plants will facilitate breeding and development of new varieties based on, for example, genetic variations of endogenous genes and/or genome editing, representing an alternative to transgenic approaches.

A glance at the chemodiversity of Ocimum species: Trends, implications, and strategies for the quality and yield improvement of essential oil.

Ocimum species represent commercially important medicinal and aromatic plants. The essential oil biosynthesized by Ocimum species is enriched with specialized metabolites specifically, terpenoids and phenylpropanoids. Interestingly, various Ocimum species are known to exhibit diverse chemical profiles, and this chemical diversity has been at the center of many studies to identify commercially important chemotypes. Here, we present various chemotypes from the Ocimum species and emphasize trends, implications, and strategies for the quality and yield improvement of essential oil. Globally, many Ocimum species have been analyzed for their essential oil composition in over 50 countries. Asia represents the highest number of chemotypes, followed by Africa, South America, and Europe. Ocimum basilicum L. has been the most widespread and well-studied species, followed by O. gratissimum L., O. tenuiflorum L., O. canum Sims, O. americanum and O. kilimandscharicum Gürke. Moreover, various molecular reasons, benefits, adverse health effects and mechanisms behind this vast chemodiversity have been discussed. Different strategies of plant breeding, metabolic engineering, transgenic, and tissue-culture, along with anatomical modifications, are surveyed to enhance specific chemotypic profiles and essential oil yield in numerous Ocimum species. Consequently, chemical characterization of the essential oil obtained from Ocimum species has become indispensable for its proper utilization. The present chemodiversity knowledge from Ocimum species will help to exploit various applications in the industrial, agriculture, biopharmaceutical, and food sectors. Supplementary Information: The online version contains supplementary material available at 10.1007/s11101-021-09767-z.

Lake Chemodiversity Driven by Natural and Anthropogenic Factors.

As extremely active sites processing terrestrially derived dissolved organic matter (DOM), lakes deserve sufficient attention. Because of high-complexity interactions between DOM and the surrounding environment, the natural and anthropogenic drivers controlling the composition and chemodiversity of DOM molecules in lakes remain unclear. Here, 13,952 DOM molecules were identified and assessed in 45 lakes across China via ultrahigh-resolution mass spectrometry. Furthermore, the effects of both natural and anthropogenic factors on the DOM composition, DOM chemodiversity, and greenhouse gas emissions were investigated. The majority of the variations in DOM chemical composition could be attributed to the differences in the hydrology and nutrient concentrations of the lakes, and human activities also played a role, mainly through atmospheric pollution. Environmental factors mainly influenced DOM chemodiversity in the form of S-containing compounds. N-containing compounds exhibited a positive correlation with CO2 emissions, while N- and S-free compounds exhibited a positive correlation with N2O emissions. These results facilitate a comprehensive understanding of the interactions between lake DOM and the surrounding environment, thereby providing a reference for the formulation of strategies aimed at the harmonious development of human and natural environments.

Expansion of the composition library for chemodiversity of hardwood extractives at molecular level by ultrahigh-resolution mass spectrometry.

To enhance the characterization of wood extractives at molecular level, a detailed ultrahigh-resolution mass spectrometry (UHRMS)-based analytical methodology was developed in this work. The analytical strategies, including selection of compatible solvent for extraction, evaluation of ionization solvent for effective electrospray ionization, and multi-dimensional data analysis, were established to ensure a comprehensive characterization of complex compositions in wood extractives. Extraction capability of seven solvents with varied polarities was examined by a standard reference material of hardwood biomass and evaluated based on thousands of compounds which were much more than those discovered before. With a variety of data-processing approaches, including compound type distribution, double bond equivalent versus carbon number plot, and van Krevelen diagram, the chemodiversity of the extractives was fully explored from different perspectives. This work greatly expanded the compound library of wood extractives and could also provide guidance for the integrated composition analysis of other biomass materials.

Investigation of Volatile Iridoid Terpenes in Nepeta cataria L. (Catnip) Genotypes.

Catnip (Nepeta cataria L.) is of scientific interest largely due to the production of nepetalactones, volatile iridoid terpenes with strong arthropod repellent activity. However, the plant can also produce other bioactive volatile iridoids, such as nepetalic acid (NA), nepetalactam (NT) and dihydronepetalactone (DHNL) that have not been studied extensively. Germplasm studies on plants that can produce such compounds are scarce. The present study evaluated the chemical diversity of catnip genotypes with a focus on NA, NT and DHNL. A total of 34 genotypes were harvested at different times over two years. The ethanolic extract of the plants was screened for iridoids by ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry. CR9 × CR3 genotype had the highest value for biomass yield, while cultivar CR9 had the highest value for accumulated NA. Genotype UK.2 had the highest value for accumulated NT yield and CR5 had the highest value for accumulated DHNL. Overall, patented cultivars and elite selections performed better than other less studied genotypes. Harvest time influenced the accumulation of secondary metabolites differentially for the genotypes. This is the first germplasm study with a focus on these iridoid compounds, yet more studies are necessary as genotype characterization is essential for breeding and standardization of products for industry.

Natural variation in the expression and catalytic activity of a naringenin 7-O-methyltransferase influences antifungal defenses in diverse rice cultivars.

Phytoalexins play a pivotal role in plant-pathogen interactions. Whereas leaves of rice (Oryza sativa) cultivar Nipponbare predominantly accumulated the phytoalexin sakuranetin after jasmonic acid induction, only very low amounts accumulated in the Kasalath cultivar. Sakuranetin is synthesized from naringenin by naringenin 7-O-methyltransferase (NOMT). Analysis of chromosome segment substitution lines and backcrossed inbred lines suggested that NOMT is the underlying cause of differential phytoalexin accumulation between Nipponbare and Kasalath. Indeed, both NOMT expression and NOMT enzymatic activity are lower in Kasalath than in Nipponbare. We identified a proline to threonine substitution in Kasalath relative to Nipponbare NOMT as the main cause of the lower enzymatic activity. Expanding this analysis to rice cultivars with varying amounts of sakuranetin collected from around the world showed that NOMT induction is correlated with sakuranetin accumulation. In bioassays with Pyricularia oryzae, Gibberella fujikuroi, Bipolaris oryzae, Burkholderia glumae, Xanthomonas oryzae, Erwinia chrysanthemi, Pseudomonas syringae, and Acidovorax avenae, naringenin was more effective against bacterial pathogens and sakuranetin was more effective against fungal pathogens. Therefore, the relative amounts of naringenin and sakuranetin may provide protection against specific pathogen profiles in different rice-growing environments. In a dendrogram of NOMT genes, those from low-sakuranetin-accumulating cultivars formed at least two clusters, only one of which involves the proline to threonine mutation, suggesting that the low sakuranetin chemotype was acquired more than once in cultivated rice. Strains of the wild rice species Oryza rufipogon also exhibited differential sakuranetin accumulation, indicating that this metabolic diversity predates rice domestication.

Allylic Hydroxylation Activity Is a Source of Saponin Chemodiversity in the Genus Glycyrrhiza.

Licorice (Glycyrrhiza) produces glycyrrhizin, a valuable triterpenoid saponin, which exhibits persistent sweetness and broad pharmacological activities. In the genus Glycyrrhiza, three species, Glycyrrhiza uralensis, Glycyrrhiza glabra and Glycyrrhiza inflata, produce glycyrrhizin as their main triterpenoid saponin, which has a ketone group at C-11. Other Glycyrrhiza species produce mainly oleanane-type saponins, which harbor homoannular or heteroannular diene structures that lack the C-11 ketone. Although the glycyrrhizin biosynthetic pathway has been fully elucidated, the pathway involving saponins with diene structures remains unclear. CYP88D6 from G. uralensis is a key enzyme in glycyrrhizin biosynthesis, catalyzing the sequential two-step oxidation of ß-amyrin at position C-11 to produce 11-oxo-ß-amyrin. In this study, we evaluated the functions of CYP88D6 homologs from the glycyrrhizin-producing species G. glabra and G. inflata and from the non-glycyrrhizin-producing species Glycyrrhiza pallidiflora and Glycyrrhiza macedonica, using yeast engineered to supply ß-amyrin as a substrate. Yeast expressing CYP88D6 homologs from glycyrrhizin-producing species produced 11-oxo-ß-amyrin. However, yeast expressing CYP88D6 homologs (such as CYP88D15) from the non-glycyrrhizin-producing Glycyrrhiza species accumulated oleana-9(11),12-dien-3ß-ol and oleana-11,13(18)-dien-3ß-ol; these diene compounds are non-enzymatic or yeast endogenous enzymatic dehydration derivatives of 11α-hydroxy-ß-amyrin, a direct reaction product of CYP88D15. These results suggest that the activities of CYP88D6 homologs, particularly their ability to catalyze the second oxidation, could influence glycyrrhizin productivity and diversify the chemical structures of saponins in Glycyrrhiza plants. A synthetic biological approach to engineer CYP88D15 could enable the production of pharmacologically active saponins with diene structures, such as saikosaponins, whose biosynthetic pathways have yet to be fully characterized.

Insights into phenolic compounds from microalgae: structural variety and complex beneficial activities from health to nutraceutics.

Phenolic compounds (PCs) are a family of secondary metabolites with recognized biological activities making them attractive for the biomedical "red" biotechnology. The development of the eco-sustainable production of natural bioactive metabolites requires using easy cultivable organisms, such as microalgae, which represents one of the most promising sources for biotechnological applications. Microalgae are photosynthetic organisms inhabiting aquatic systems, displaying high levels of biological and functional diversities, and are well-known producers of fatty acids and carotenoids. They are also rich in other families of bioactive molecules e.g. phenolic compounds. Microalgal PCs however are less investigated than other molecular components. This study aims to provide a state-of-art picture of the actual knowledge on microalgal phenolic compounds, reviewing information on the PC content variety and chemodiversity in microalgae, their environmental modulation, and we aim to report discuss data on PC biosynthetic pathways. We report the challenges of promoting microalgae as a relevant source of natural PCs, further enhancing the interests of microalgal "biofactories" for biotechnological applications (i.e. nutraceutical, pharmacological, or cosmeceutical products).

Insights into the Variation in Bioactivities of Closely Related Streptomyces Strains from Marine Sediments of the Visayan Sea against ESKAPE and Ovarian Cancer.

Marine sediments host diverse actinomycetes that serve as a source of new natural products to combat infectious diseases and cancer. Here, we report the biodiversity, bioactivities against ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and ovarian cancer, and metabolites variation among culturable actinomycetes isolated from the marine sediments of Visayan Sea, Philippines. We identified 15 Streptomyces species based on a 16S rRNA gene sequence analysis. The crude extracts of 10 Streptomyces species have inhibited the growth of ESKAPE pathogens with minimum inhibitory concentration (MIC) values ranging from 0.312 mg/mL to 20 mg/mL depending on the strain and pathogens targeted. Additionally, ten crude extracts have antiproliferative activity against A2780 human ovarian carcinoma at 2 mg/mL. To highlight, we observed that four phylogenetically identical Streptomyces albogriseolus strains demonstrated variation in antibiotic and anticancer activities. These strains harbored type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes in their genomes, implying that their bioactivity is independent of the polymerase chain reaction (PCR)-detected bio-synthetic gene clusters (BGCs) in this study. Metabolite profiling revealed that the taxonomically identical strains produced core and strain-specific metabolites. Thus, the chemical diversity among these strains influences the variation observed in their biological activities. This study expanded our knowledge on the potential of marine-derived Streptomyces residing from the unexplored regions of the Visayan Sea as a source of small molecules against ESKAPE pathogens and cancer. It also highlights that Streptomyces species strains produce unique strain-specific secondary metabolites; thus, offering new chemical space for natural product discovery.