Multi-Omics Analysis of Lipid Metabolism for a Marine Probiotic Meyerozyma guilliermondii GXDK6 Under High NaCl Stress

Investigating microbial lipid regulation contributes to understanding the lipid-dependent signal transduction process of cells and helps to improve the sensitivity of microorganisms to environmental factors by interfering with lipid metabolism, thus beneficial for constructing advanced cell factories of novel molecular drugs. Integrated omics technology was used to systematically reveal the lipid metabolism mechanism of a marine Meyerozyma guilliermondii GXDK6 under high NaCl stress and test the sensitivity of GXDK6 to antibiotics when its lipid metabolism transformed. The omics data showed that when GXDK6 perceived 10% NaCl stress, the expression of AYR1 and NADPH-dependent 1-acyldihydroxyacetone phosphate reductase was inhibited, which weaken the budding and proliferation of cell membranes. This finding was further validated by decreased 64.39% of OD600 under 10% NaCl stress when compared with salt-free stress. In addition, salt stress promoted a large intracellular accumulation of glycerol, which was also verified by exogenous addition of glycerol. Moreover, NaCl stress remarkably inhibited the expression of drug target proteins (such as lanosterol 14-alpha demethylase), thereby increasing sensitivity to fluconazole. This study provided new insights into the molecular mechanism involved in the regulation of lipid metabolism in Meyerozyma guilliermondii strain and contributed to developing new methods to improve the effectiveness of killing fungi with lower antibiotics.

Microbial Systems Ecology to Understand Cross-Feeding in Microbiomes

Understanding how microorganism-microorganism interactions shape microbial assemblages is a key to deciphering the evolution of dependencies and co-existence in complex microbiomes. Metabolic dependencies in cross-feeding exist in microbial communities and can at least partially determine microbial community composition. To parry the complexity and experimental limitations caused by the large number of possible interactions, new concepts from systems biology aim to decipher how the components of a system interact with each other. The idea that cross-feeding does impact microbiome assemblages has developed both theoretically and empirically, following a systems biology framework applied to microbial communities, formalized as microbial systems ecology (MSE) and relying on integrated-omics data. This framework merges cellular and community scales and offers new avenues to untangle microbial coexistence primarily by metabolic modeling, one of the main approaches used for mechanistic studies. In this mini-review, we first give a concise explanation of microbial cross-feeding. We then discuss how MSE can enable progress in microbial research. Finally, we provide an overview of a MSE framework mostly based on genome-scale metabolic-network reconstruction that combines top-down and bottom-up approaches to assess the molecular mechanisms of deterministic processes of microbial community assembly that is particularly suitable for use in synthetic biology and microbiome engineering.

Cross-Feeding between Cyanobacterium Synechococcus and Escherichia Coli in Artificial Autotrophic-Heterotrophic Co-Culture System Revealed by Integrated Omics Analysis

Background: The light-driven consortia consisted of sucrose-secreting cyanobacteria and heterotrophic species capable of producing valuable chemicals have recently attracted significant attention, and are considered as a promising strategy for green biomanufacturing. In a previous study (Zhang et al, 2020, Biotechnol Biofuel, 13:82), we achieved a one-step conversion of CO2 through sucrose derived from cyanobacteria to fine chemicals by constructing an artificial co-culture system consisting of sucrose-secreting Synechococcus elongateus cscB+ and 3-hydroxypropionic acid (3-HP) producing Escherichia coli ABKm. Analysis of the co-culture system showed that cyanobacterial cells were growing better than its corresponding axenic culture. To explore the underlaid mechanism and to identify the metabolic modules to further improve the co-culture system, an integrated metabolomics, transcriptomic and proteomic analysis was conducted.Results: We first explored the effect of reactive oxygen species (ROS) on cyanobacterial cell growth under co-culture system by supplementing additional ascorbic acid to scavenge ROS in CoBG-11 medium. The result showed cyanobacterial growth was obviously improved with additional 1 mM ascorbic acid under pure culture; however, cyanobacterial growth was still slower than that in the co-culture with E. coli, suggesting that the better growth of Synechococcus cscB+ might be caused by other factors more than just ROS quenching. We then investigated the intracellular metabolite levels in cyanobacteria using LC-MS based metabolomics analysis. The results showed that metabolites involved in central carbon metabolism were increased, suggesting more carbon sources were utilized by cyanobacteria in the co-culture system, which illuminating that enhanced photosynthesis attributes to the higher CO2 availability produced from co-cultivated heterotrophic partner. To further explore the interaction based on cross-feeding and metabolite exchange, quantitative transcriptomics and proteomics were applied to Synechococcus cscB+. Analysis of differentially regulated genes/proteins showed that the higher availability of carbon, nitrogen, phosphate, calcium, Cu2+, Fe3+ and co-factors was observed in co-cultivated Synechococcus cscB+ during co-cultivation, suggesting the heterotrophic partner in the system might be involved in supplementing CO2 and improving essential micronutrients necessary to maintain high photosynthetic growth of Synechococcus cscB+. Conclusion: Integrated omics analysis of the interaction mechanism between S. elongateus and E. coli showed metabolic changes such as enhanced photosynthesis, oxidative phosphorylation, essential micronutrients, and the ROS scavenging occurred at multiple levels of genes, proteins and metabolites, which might be together contributing to the better cell growth of Synechococcus cscB+ in co-cultivation. In addition, the results implicated that the co-culture system could be further improved by engineering the modules related to the ROS quenching, carbon metabolism, nitrogen metabolism, Pi transport, metal transport and co-factors biosynthesis. Finally, the light condition, which may influence the cross-feeding metabolites between phototrophic and heterotrophic species, and also affect the oxidative pressure on the E. coli strains due to the photosynthesis, could be further optimized to improve cell growth in the co-culture system, eventually leading to high productivity of value-added products.

Integrated Omics Approach to Unveil Antifungal Bacterial Polyynes as acetyl-CoA Acetyltransferase Inhibitors

Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for the development of antifungal agents.

An integrated host-microbiome response to atrazine exposure mediates toxicity in Drosophila

The gut microbiome produces vitamins, nutrients, and neurotransmitters, and helps to modulate the host immune system—and also plays a major role in the metabolism of many exogenous compounds, including drugs and chemical toxicants. However, the extent to which specific microbial species or communities modulate hazard upon exposure to chemicals remains largely opaque. Focusing on the effects of collateral dietary exposure to the widely used herbicide atrazine, we applied integrated omics and phenotypic screening to assess the role of the gut microbiome in modulating host resilience in Drosophila melanogaster. Transcriptional and metabolic responses to these compounds are sex-specific and depend strongly on the presence of the commensal microbiome. Sequencing the genomes of all abundant microbes in the fly gut revealed an enzymatic pathway responsible for atrazine detoxification unique to Acetobacter tropicalis. We find that Acetobacter tropicalis alone, in gnotobiotic animals, is sufficient to rescue increased atrazine toxicity to wild-type, conventionally reared levels. This work points toward the derivation of biotic strategies to improve host resilience to environmental chemical exposures, and illustrates the power of integrative omics to identify pathways responsible for adverse health outcomes.

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

Immunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far. A significant focus to date has been the identification of specific markers associated with response to immunotherapy. Unfortunately, the heterogeneity between patients and cancer types means identifying markers of response to therapy is inherently complex. There is a growing appreciation for the role of the tumour microenvironment (TME) in directing response to immunotherapy. The TME is highly heterogeneous and contains immune, stromal, vascular and tumour cells that all communicate and interact with one another to form solid tumours. This review analyses major cell populations present within the TME with a focus on their diverse and often contradictory roles in cancer and how this informs our understanding of immunotherapy. Furthermore, we discuss the role of integrated omics in providing a comprehensive view of the TME and demonstrate the potential of leveraging multi-omics to decipher the underlying mechanisms of anti-tumour immunity for the development of novel immunotherapeutic strategies.

Copper Tolerance Mechanism of the Novel Marine Multi-Stress Tolerant Yeast Meyerozyma guilliermondii GXDK6 as Revealed by Integrated Omics Analysis

Various agricultural products used in food fermentation are polluted by heavy metals, especially copper, which seriously endangers human health. Methods to remove copper with microbial strategies have gained interests. A novel Meyerozyma guilliermondii GXDK6 could survive independently under high stress of copper (1400 ppm). The copper tolerance mechanism of GXDK6 was revealed by integrated omics in this work. Whole-genome analysis showed that nine genes (i.e., CCC2, CTR3, FRE2, GGT, GST, CAT, SOD2, PXMP4, and HSP82) were related to GXDK6 copper tolerance. Copper stress elevated glutathione metabolism-related gene expression, glutathione content, and glutathione sulfur transferase activity, suggesting enhanced copper conjugation and detoxification in cells. The inhibited copper uptake by Ctr3 and enhanced copper efflux by Ccc2 contributed to the decrease in intracellular copper concentration. The improved expression of antioxidant enzyme genes (PXMP4, SOD2, and CAT), accompanied by the enhanced activities of antioxidant enzymes (peroxidase, superoxide dismutase, and catalase), decreased copper-induced reactive oxygen species production, protein carbonylation, lipid peroxidation, and cell death. The metabolite D-mannose against harsh stress conditions was beneficial to improving copper tolerance. This study contributed to understanding the copper tolerance mechanism of M. guilliermondii and its application in removing copper during fermentation.

Omics Technologies to Enhance Plant Based Functional Foods: An Overview

Functional foods are natural products of plants that have health benefits beyond necessary nutrition. Functional foods are abundant in fruits, vegetables, spices, beverages and some are found in cereals, millets, pulses and oilseeds. Efforts to identify functional foods in our diet and their beneficial aspects are limited to few crops. Advances in sequencing and availability of different omics technologies have given opportunity to utilize these tools to enhance the functional components of the foods, thus ensuring the nutritional security. Integrated omics approaches including genomics, transcriptomics, proteomics, metabolomics coupled with artificial intelligence and machine learning approaches can be used to improve the crops. This review provides insights into omics studies that are carried out to find the active components and crop improvement by enhancing the functional compounds in different plants including cereals, millets, pulses, oilseeds, fruits, vegetables, spices, beverages and medicinal plants. There is a need to characterize functional foods that are being used in traditional medicines, as well as utilization of this knowledge to improve the staple foods in order to tackle malnutrition and hunger more effectively.

Organ-specific, integrated omics data-based study on the metabolic pathways of the medicinal plant Bletilla striata (Orchidaceae)

Background Bletilla striata is one of the important species belonging to the Bletilla genus of Orchidaceae. Since its extracts have an astringent effect on human tissues, B. striata is widely used for hemostasis and healing. Recently, some other beneficial effects have also been uncovered, such as antioxidation, antiinflammation, antifibrotic, and immunomodulatory activities. As a key step towards a thorough understanding on the medicinal ingredient production in B. striata, deciphering the regulatory codes of the metabolic pathways becomes a major task. Results In this study, three organs (roots, tubers and leaves) of B. striata were analyzed by integrating transcriptome sequencing and untargeted metabolic profiling data. Five different metabolic pathways, involved in polysaccharide, sterol, flavonoid, terpenoid and alkaloid biosynthesis, were investigated respectively. For each pathway, the expression patterns of the enzyme-coding genes and the accumulation levels of the metabolic intermediates were presented in an organ-specific way. Furthermore, the relationships between enzyme activities and the levels of the related metabolites were partially inferred. Within the biosynthetic pathways of polysaccharides and flavonoids, long-range phytochemical transportation was proposed for certain metabolic intermediates and/or the enzymes. Conclusions The data presented by this work could strengthen the molecular basis for further studies on breeding and medicinal uses of B. striata.

Overview of Metabolomic Analysis and the Integration with Multi-Omics for Economic Traits in Cattle

Metabolomics has been applied to measure the dynamic metabolic responses, to understand the systematic biological networks, to reveal the potential genetic architecture, etc., for human diseases and livestock traits. For example, the current published results include the detected relevant candidate metabolites, identified metabolic pathways, potential systematic networks, etc., for different cattle traits that can be applied for further metabolomic and integrated omics studies. Therefore, summarizing the applications of metabolomics for economic traits is required in cattle. We here provide a comprehensive review about metabolomic analysis and its integration with other omics in five aspects: (1) characterization of the metabolomic profile of cattle; (2) metabolomic applications in cattle; (3) integrated metabolomic analysis with other omics; (4) methods and tools in metabolomic analysis; and (5) further potentialities. The review aims to investigate the existing metabolomic studies by highlighting the results in cattle, integrated with other omics studies, to understand the metabolic mechanisms underlying the economic traits and to provide useful information for further research and practical breeding programs in cattle.