Iran J Parasitol. 2021 Jan-Mar;16(1):151-158. doi: 10.18502/ijpa.v16i1.5535.

ABSTRACT

BACKGROUND: Due to numerous side effects of common drugs in treatment of leishmaniasis, new therapeutic approaches focus on herbal compounds. Therefore, we aimed to determine the effect of crocin and stigmasterol on in-vitro growth of promastigotes and amastigotes of Leishmania major in the Department of Parasitology, Pasteur Institute, Tehran, Iran in 2018.

METHODS: The effect of different concentrations of crocin and stigmasterol were evaluated by determining their in-vitro inhibitory effects on promastigotes and amastigotes of the L. major using MTT assay.

RESULTS: The fatality rate was 65.27% and 71.96% for crocin and stigmasterol respectively at 24 h post-culture in concentration of 50 μg/mL. The mean inhibitory effect of crocin and stigmasterol on L major amastigotes after 72 h were 52.22% and 38.96%.

CONCLUSION: The crocin and stigmasterol had efficient adverse effects on promastigote and amastigotes of L. major, hence, further studies on the anti-leishmanial effects of these herbal compounds in human and animal models are recommended.

PMID:33786057 | PMC:PMC7988674 | DOI:10.18502/ijpa.v16i1.5535

Nat Commun. 2021 Mar 30;12(1):1975. doi: 10.1038/s41467-021-22092-5.

ABSTRACT

The steady-state size of bacterial cells correlates with nutrient-determined growth rate. Here, we explore how rod-shaped bacterial cells regulate their morphology during rapid environmental changes. We quantify cellular dimensions throughout passage cycles of stationary-phase cells diluted into fresh medium and grown back to saturation. We find that cells exhibit characteristic dynamics in surface area to volume ratio (SA/V), which are conserved across genetic and chemical perturbations as well as across species and growth temperatures. A mathematical model with a single fitting parameter (the time delay between surface and volume synthesis) is quantitatively consistent with our SA/V experimental observations. The model supports that this time delay is due to differential expression of volume and surface-related genes, and that the first division after dilution occurs at a tightly controlled SA/V. Our minimal model thus provides insight into the connections between bacterial growth rate and cell shape in dynamic environments.

PMID:33785742 | DOI:10.1038/s41467-021-22092-5

mBio. 2021 Mar 30;12(2):e00023-21. doi: 10.1128/mBio.00023-21.

ABSTRACT

Infection with the obligate intracellular bacterium Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. Since no vaccine is available to date, antimicrobial therapy is the only alternative in C. trachomatis infection. However, changes in chlamydial replicative activity and the occurrence of chlamydial persistence caused by diverse stimuli have been proven to impair treatment effectiveness. Here, we report the mechanism for C. trachomatis regulating host signaling processes and mitochondrial function, which can be used for chlamydial metabolic reprogramming during treatment with β-lactam antimicrobials. Activation of signal transducer and activator of transcription 3 (STAT3) is a well-known host response in various bacterial and viral infections. In C. trachomatis infection, inactivation of STAT3 by host protein tyrosine phosphatases increased mitochondrial respiration in both the absence and presence of β-lactam antimicrobials. However, during treatment with β-lactam antimicrobials, C. trachomatis increased the production of citrate as well as the activity of host ATP-citrate lyase involved in fatty acid synthesis. Concomitantly, chlamydial metabolism switched from the tricarboxylic acid cycle to fatty acid synthesis. This metabolic switch was a unique response in treatment with β-lactam antimicrobials and was not observed in gamma interferon (IFN-γ)-induced persistent infection. Inhibition of fatty acid synthesis was able to attenuate β-lactam-induced chlamydial persistence. Our findings highlight the importance of the mitochondrion-fatty acid interplay for the metabolic reprogramming of C. trachomatis during treatment with β-lactam antimicrobials.IMPORTANCE The mitochondrion generates most of the ATP in eukaryotic cells, and its activity is used for controlling the intracellular growth of Chlamydia trachomatis Furthermore, mitochondrial activity is tightly connected to host fatty acid synthesis that is indispensable for chlamydial membrane biogenesis. Phospholipids, which are composed of fatty acids, are the central components of the bacterial membrane and play a crucial role in the protection against antimicrobials. Chlamydial persistence that is induced by various stimuli is clinically relevant. While one of the well-recognized inducers, β-lactam antimicrobials, has been used to characterize chlamydial persistence, little is known about the role of mitochondria in persistent infection. Here, we demonstrate how C. trachomatis undergoes metabolic reprogramming to switch from the tricarboxylic acid cycle to fatty acid synthesis with promoted host mitochondrial activity in response to treatment with β-lactam antimicrobials.

PMID:33785629 | DOI:10.1128/mBio.00023-21

mBio. 2021 Mar 30;12(2):e00390-21. doi: 10.1128/mBio.00390-21.

ABSTRACT

When engaging in symbiosis with legume hosts, rhizobia are confronted with environmental changes, including nutrient availability and stress exposure. Genetic circuits allow responding to these environmental stimuli to optimize physiological adaptations during the switch from the free-living to the symbiotic life style. A pivotal regulatory system of the nitrogen-fixing soybean endosymbiont Bradyrhizobium diazoefficiens for efficient symbiosis is the general stress response (GSR), which relies on the alternative sigma factor σEcfG However, the GSR-controlled process required for symbiosis has not been identified. Here, we demonstrate that biosynthesis of trehalose is under GSR control, and mutants lacking the respective biosynthetic genes otsA and/or otsB phenocopy GSR-deficient mutants under symbiotic and selected free-living stress conditions. The role of trehalose as a cytoplasmic chemical chaperone and stress protectant can be functionally replaced in an otsA or otsB mutant by introducing heterologous genetic pathways for biosynthesis of the chemically unrelated compatible solutes glycine betaine and (hydroxy)ectoine. Alternatively, uptake of exogenously provided trehalose also restores efficient symbiosis and tolerance to hyperosmotic and hyperionic stress of otsA mutants. Hence, elevated cytoplasmic trehalose levels resulting from GSR-controlled biosynthesis are crucial for B. diazoefficiens cells to overcome adverse conditions during early stages of host infection and ensure synchronization with root nodule development.IMPORTANCE The Bradyrhizobium-soybean symbiosis is of great agricultural significance and serves as a model system for fundamental research in bacterium-plant interactions. While detailed molecular insight is available about mutual recognition and early nodule organogenesis, our understanding of the host-imposed conditions and the physiology of infecting rhizobia during the transition from a free-living state in the rhizosphere to endosymbiotic bacteroids is currently limited. In this study, we show that the requirement of the rhizobial general stress response (GSR) during host infection is attributable to GSR-controlled biosynthesis of trehalose. Specifically, trehalose is crucial for an efficient symbiosis by acting as a chemical chaperone to protect rhizobia from osmostress during host infection.

PMID:33785618 | DOI:10.1128/mBio.00390-21

mSystems. 2021 Mar 30;6(2):e00820-20. doi: 10.1128/mSystems.00820-20.

ABSTRACT

Immune response is a highly coordinated cascade involving all the subsets of peripheral blood mononuclear cells (PBMCs). In this study, RNA sequencing (RNA-Seq) analysis of PBMC subsets was done to delineate the systems biology behind immune protection of the vaccine in sheep and goats. The PBMC subsets studied were CD4+, CD8+, CD14+, CD21+, and CD335+ cells from day 0 and day 5 of sheep and goats vaccinated with Sungri/96 peste des petits ruminants virus. Assessment of the immune response processes enriched by the differentially expressed genes (DEGs) in all the subsets suggested a strong dysregulation toward the development of early inflammatory microenvironment, which is very much required for differentiation of monocytes to macrophages, and activation as well as the migration of dendritic cells into the draining lymph nodes. The protein-protein interaction networks among the antiviral molecules (IFIT3, ISG15, MX1, MX2, RSAD2, ISG20, IFIT5, and IFIT1) and common DEGs across PBMC subsets in both species identified ISG15 to be a ubiquitous hub that helps in orchestrating antiviral host response against peste des petits ruminants virus (PPRV). IRF7 was found to be the key master regulator activated in most of the subsets in sheep and goats. Most of the pathways were found to be inactivated in B lymphocytes of both the species, indicating that 5 days postvaccination (dpv) is too early a time point for the B lymphocytes to react. The cell-mediated immune response and humoral immune response pathways were found more enriched in goats than in sheep. Although animals from both species survived the challenge, a contrast in pathway activation was observed in CD335+ cells.IMPORTANCE Peste des petits ruminants (PPR) by PPR virus (PPRV) is an World Organisation for Animal Health (OIE)-listed acute, contagious transboundary viral disease of small ruminants. The attenuated Sungri/96 PPRV vaccine used all over India against this PPR provides long-lasting robust innate and adaptive immune response. The early antiviral response was found mediated through type I interferon-independent interferon-stimulated gene (ISG) expression. However, systems biology behind this immune response is unknown. In this study, in vivo transcriptome profiling of PBMC subsets (CD4+, CD8+, CD14+, CD21+, and CD335+) in vaccinated goats and sheep (at 5 days postvaccination) was done to understand this systems biology. Though there are a few differences in the systems biology across cells (specially the NK cells) between sheep and goats, the coordinated response that is inclusive of all the cell subsets was found to be toward the induction of a strong innate immune response, which is needed for an appropriate adaptive immune response.

PMID:33785572 | DOI:10.1128/mSystems.00820-20

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 27:110317. doi: 10.1016/j.pnpbp.2021.110317. Online ahead of print.

ABSTRACT

Neurological and psychiatric side effects accompany the high-dose interferon-alpha (IFNA) therapy. The primary genes responsible for these complications are mostly unknown. Our genome-wide search in mouse and rat genomes for the conservative genes containing IFN-stimulated response elements (ISRE) in their promoters revealed a new potential target gene of IFNA, Grin3α, which encodes the 3A subunit of NMDA receptor. This study aimed to explore the impact of IFNA on the expression of Grin3α and Ifnα genes and neurotransmitters endo/exocytosis in the mouse brain. We administered recombinant human IFN-alpha 2b (rhIFN-α2b) intracranially, and 24 h later, we isolated six brain regions and used the samples for RT-qPCR and western blot analysis. Synaptosomes were isolated from the cortex to analyze endo/exocytosis with acridine orange and L-[14C]glutamate. IFNA induced an increase in Grin3α mRNA and GRIN3A protein, but a decrease in Ifnα mRNA and protein. IFNA did not affect the accumulation and distribution of L-[14C]glutamate and acridine orange between synaptosomes and the extra-synaptosomal space. It caused the more significant acridine orange release activated by NMDA or glutamate than from control mice's synaptosomes. In response to IFNA, the newly discovered association between elevated Grin3α expression and NMDA- and glutamate-evoked neurotransmitters release from synaptosomes implies a new molecular mechanism of IFNA neurotoxicity.

PMID:33785426 | DOI:10.1016/j.pnpbp.2021.110317

J Biol Chem. 2021 Mar 27:100603. doi: 10.1016/j.jbc.2021.100603. Online ahead of print.

ABSTRACT

Organic anion transporter 1 (OAT1/SLC22A6) is a drug transporter with numerous xenobiotic and endogenous substrates. The Remote Sensing and Signaling Theory suggests that drug transporters with compatible ligand preferences can play a role in "organ crosstalk," mediating overall organismal communication. Other drug transporters are well known to transport lipids, but surprisingly little is known about the role of OAT1 in lipid metabolism. To explore this subject, we constructed a genome-scale metabolic model using omics data from the Oat1 knockout mouse. The model implicated OAT1 in the regulation of many classes of lipids, including fatty acids, bile acids, and prostaglandins. Accordingly, serum metabolomics of Oat1 knockout mice revealed increased polyunsaturated fatty acids, diacylglycerols, and long chain fatty acids, and decreased ceramides and bile acids when compared to wild type controls. Some aged knockout mice also displayed increased lipid droplets in the liver when compared to wild type mice. Chemoinformatics and machine learning analyses of these altered lipids defined molecular properties that form the structural basis for lipid-transporter interactions, including the number of rings, positive charge/volume, and complexity of the lipids. Finally, we obtained targeted serum metabolomics data after short-term treatment of rodents with the OAT-inhibiting drug probenecid to identify potential drug-metabolite interactions. The treatment resulted in alterations in eicosanoids and fatty acids, further supporting our metabolic reconstruction predictions. Consistent with the Remote Sensing and Signaling Theory, the data support a role of OAT1 in systemic lipid metabolism.

PMID:33785360 | DOI:10.1016/j.jbc.2021.100603

Clin Epigenetics. 2021 Mar 30;13(1):66. doi: 10.1186/s13148-021-01047-z.

ABSTRACT

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients. Here, we provide an overview of clinical epigenetics within the context of network analysis. We illustrate achievements to date and discuss how we can move from traditional medicine into the era of network medicine (NM), where pathway-informed molecular diagnostics will allow treatment selection following the paradigm of precision medicine.

PMID:33785068 | DOI:10.1186/s13148-021-01047-z

Proc Biol Sci. 2021 Mar 31;288(1947):20210418. doi: 10.1098/rspb.2021.0418. Epub 2021 Mar 31.

ABSTRACT

The bitter taste sensation is important to warn mammals of the ingestion of potentially toxic food compounds. For mammals, whose nutrition relies on highly specific food sources, such as blood in the case of vampire bats, it is unknown if bitter sensing is involved in prey selection. By contrast to other bat species, vampire bats exhibit numerous bitter taste receptor pseudogenes, which could point to a decreased importance of bitter taste. However, electrophysiological and behavioural studies suggest the existence of functional bitter taste transmission. To determine the agonist spectra of the three bitter taste receptors that are conserved in all three vampire bat species, we investigated the in vitro activation of Desmodus rotundus T2R1, T2R4 and T2R7. Using a set of 57 natural and synthetic bitter compounds, we were able to identify agonists for all three receptors. Hence, we confirmed a persisting functionality and, consequently, a putative biological role of bitter taste receptors in vampire bats. Furthermore, the activation of the human TAS2R7 by metal ions is shown to be conserved in D. rotundus.

PMID:33784867 | DOI:10.1098/rspb.2021.0418

Mol Biol Evol. 2021 Mar 30:msab078. doi: 10.1093/molbev/msab078. Online ahead of print.

ABSTRACT

Native cattle breeds represent an important cultural heritage. They are a reservoir of genetic variation useful for properly responding to agriculture needs in light of ongoing climate changes. Evolutionary processes that occur in response to extreme environmental conditions could also be better understood using adapted local populations. Herein, different evolutionary histories of the world northernmost native cattle breeds from Russia were investigated. They highlighted Kholmogory as a typical taurine cattle, while Yakut cattle separated from European taurines ∼5,000 years ago and contain numerous ancestral and some novel genetic variants allowing their adaptation to harsh conditions of living above the Polar Circle. Scans for selection signatures pointed to several common gene pathways related to adaptation to harsh climates in both breeds. But genes affected by selection from these pathways were mostly different. A Yakut cattle breed-specific missense mutation in a highly conserved NRAP gene, represents a unique example of a young amino acid residue convergent change shared with at least 16 species of hibernating/cold-adapted mammals from six distinct phylogenetic orders. This suggests a convergent evolution event along the mammalian phylogenetic tree and fast fixation in a single isolated cattle population exposed to a harsh climate.

PMID:33784744 | DOI:10.1093/molbev/msab078

Neoplasia. 2021 Mar 27;23(4):391-399. doi: 10.1016/j.neo.2021.02.003. Online ahead of print.

ABSTRACT

Notwithstanding that high rates of glucose uptake and glycolysis are common in neoplasia, pharmacological efforts to inhibit glucose utilization for cancer treatment have not been successful. Recent evidence suggests that in addition to classical glucose transporters, sodium-glucose transporters (SGLTs) are expressed by cancers. We therefore investigated the possibility that SGLT inhibitors, which are used in treatment of type 2 diabetes, may exert antineoplastic activity by limiting glucose uptake. We show that the SGLT2 inhibitor canagliflozin inhibits proliferation of breast cancer cells. Surprisingly, the antiproliferative effects of canagliflozin are not affected by glucose availability nor by the level of expression of SGLT2. Canagliflozin reduces oxygen consumption and glutamine metabolism through the citric acid cycle. The antiproliferative effects of canagliflozin are linked to inhibition of glutamine metabolism that fuels respiration, which represents a previously unanticipated mechanism of its potential antineoplastic action.

PMID:33784591 | DOI:10.1016/j.neo.2021.02.003

Microb Biotechnol. 2021 Mar 30. doi: 10.1111/1751-7915.13808. Online ahead of print.

ABSTRACT

Industrial biotechnology gene expression systems relay on constitutive promoters compromising cellular growth from the start of the bioprocess, or on inducible devices, which require manual addition of cognate inducers. To overcome this shortcoming, we engineered an automata regulatory system based on cell-stress mechanisms. Specifically, we engineered a synthetic and highly portable phosphate-depletion library of promoters inspired by bacterial PHO starvation system (Pliar promoters). Furthermore, we fully characterized 10 synthetic promoters within the background of two well-known bacterial workhorses such as E. coli W and P. putida KT2440. The promoters displayed an interesting host-dependent performance and a wide strength spectrum ranging from 0.4- to 1.3-fold when compared to the wild-type phosphatase alkaline promoter (PphoA). By comparing with available gene expression systems, we proved the suitability of this new library for the automata and effective decoupling of growth from production in P. putida. Growth phase-dependent expression of these promoters could therefore be activated by fine tuning the initial concentration of phosphate in the medium. Finally, the Pliar library was implemented in the SEVA platform in a ready-to-use mode allowing its broad use by the scientific community.

PMID:33783967 | DOI:10.1111/1751-7915.13808

Plant J. 2021 Mar 30. doi: 10.1111/tpj.15254. Online ahead of print.

ABSTRACT

Our modern understanding of diel cell regulation in plants stems from foundational work in the late 90s that analysed the dynamics of selected genes and mutants in Arabidopsis. The subsequent rise of transcriptomics technologies such as microarrays and RNA sequencing has substantially grown our understanding of anticipatory (circadian) and reactive (light or dark triggered) diel events in plants. However, it is also becoming clear that gene expression data fails to capture critical events in diel regulation that can only be explained by studying protein-level dynamics. Over the past decade, mass spectrometry technologies and quantitative proteomic workflows have significantly advanced, finally allowing scientists to characterise diel protein regulation at high throughput. Initial proteomic investigations suggest that the diel transcriptome and proteome generally lack synchrony and that the timing of daily regulatory events in plants is impacted by multiple levels of protein regulation (e.g., post-translational modifications; PTMs and protein-protein interactions; PPIs). Here, we highlight and summarize how the use of quantitative proteomics to elucidate diel plant cell regulation has advanced our understanding of these processes. We argue that this new understanding, coupled with the extraordinary developments in mass spectrometry technologies demand greater focus on protein-level regulation of, and by, the circadian clock. This includes hitherto unexplored diel dynamics of protein turnover, PTMs, protein subcellular localization, and PPIs that can be masked by simple transcript- and protein-level changes. Finally, we propose new directions for how the latest advancements in quantitative proteomics can be utilized to answer outstanding questions in plant chronobiology.

PMID:33783885 | DOI:10.1111/tpj.15254

Environ Sci Pollut Res Int. 2021 Mar 30. doi: 10.1007/s11356-021-13662-7. Online ahead of print.

ABSTRACT

Microplastics are contaminants of great concern all over the world. Microplastics constitute pollutants themselves; moreover, other contaminants such as metals are easily absorbed on their plastic surface, becoming bioavailable to marine biota such as zooplankton.We collected marine zooplankton from Mediterranean Sea to investigate trace elements associated with microplastics. Samples were subjected to visual sorting by a stereomicroscope, collected with sterile tweezers, pooled and subjected to sonication, filtration, and drying before being subjected to acid extraction. An ICP-MS was utilized for multi-elemental determination.Aluminum, iron, chromium, zinc, nickel, molybdenum, manganese, lead cobalt, and copper were found at concentrations of mg/kg while arsenic, vanadium, rubidium, and cadmium at level of μg kg-1. Other elements such as silver, beryllium, bismuth, selenium, tin, and thallium were under the limit of quantitation. Lower levels of iron and manganese in samples from Italy were found in comparison to England and Brazil, while aluminum, copper, and zinc registered comparable values. The presence of metals in marine waters is strictly related to sediment lithology and anthropogenic inputs, but plastic plays a key role as vectors for metal ions in the marine system, being able to concentrate metals several order of magnitude higher than in surrounding waters and exerting potential toxicity for living beings after chronic exposure.

PMID:33783703 | DOI:10.1007/s11356-021-13662-7

Psychopharmacology (Berl). 2021 Mar 30. doi: 10.1007/s00213-021-05810-1. Online ahead of print.

ABSTRACT

RATIONALE: Aberrant approach-avoidance conflict processing may contribute to compulsive seeking that characterizes addiction. Exploration of the relationship between drugs of abuse and approach-avoidance behavior remains limited, especially with ethanol.

OBJECTIVES: To investigate the effects of voluntary ethanol consumption on approach-avoidance conflict behavior and to examine the potential approach/avoidance bias to predict drinking in male and female rats.

METHODS: Long-Evans rats consumed ethanol for 5 weeks under the intermittent access two-bottle choice (IA2BC) paradigm. Approach-avoidance tendencies were assessed before and after IA2BC drinking using a previously established cued approach-avoidance conflict maze task and the elevated plus maze (EPM).

RESULTS: Female rats displayed higher consumption of and preference for ethanol than males. In the conflict task, males showed greater approach bias towards cues predicting conflict than females. In females only, a median split and regression analysis of cued-conflict preference scores revealed that the more conflict-avoidant group displayed higher intake and preference for ethanol in the first few weeks of drinking. In both sexes, ethanol drinking did not affect cued-conflict preference, but ethanol exposure led to increased time spent in the central hub in the males only. Finally, anxiety levels in EPM predicted subsequent onset of ethanol drinking in males only.

CONCLUSIONS: Our results highlight sex and individual differences in both drinking and approach-avoidance bias in the face of cued conflict and further suggest that cued-conflict preference should be examined as a potential predictor of ethanol drinking. Ethanol exposure may also affect the timing of decision-making in the face of conflict.

PMID:33783557 | DOI:10.1007/s00213-021-05810-1

Epigenetics. 2021 Mar 30:1-21. doi: 10.1080/15592294.2021.1900027. Online ahead of print.

ABSTRACT

The mammalian kidney has extensive repair capacity; however, identifying adult renal stem cells has proven elusive. We applied an epigenetic marker of foetal cell origin (FCO) in diverse human tissues as a probe for developmental cell persistence, finding a 5.4-fold greater FCO proportion in kidney. Normal kidney FCO proportions averaged 49% with extensive interindividual variation. FCO proportions were significantly negatively correlated with immune-related gene expression and positively correlated with genes expressed in the renal medulla, including those involved in renal organogenesis (e.g., FGF2, PAX8, and HOXB7). FCO associated genes also mapped to medullary nephron segments in mouse and rat, suggesting evolutionary conservation of this cellular compartment. Renal cancer patients whose tumours contained non-zero FCO scores survived longer. The kidney appears unique in possessing substantial foetal epigenetic features. Further study of FCO-related gene methylation may elucidate regenerative regulatory programmes in tissues without apparent discrete stem cell compartments.

PMID:33783321 | DOI:10.1080/15592294.2021.1900027

Sheng Wu Gong Cheng Xue Bao. 2021 Mar 25;37(3):991-1003. doi: 10.13345/j.cjb.200667.

ABSTRACT

Since microdroplets are able to be generated rapidly in large amount and each droplet can be well controlled as an independent micro-cultivator, droplet microfluidic technology can be potentially used in the culture of microorganisms, and provide the microbial culture with high throughput manner. But its application mostly stays in the laboratory-level building and using for scientific research, and the wide use of droplet microfluidics in microbial technology has been limited by the key problems that the operation for microdroplets needs high technical requirements with wide affecting factors and the difficulties in integration of automatic microdroplet instrumentation. In this study, by realizing and integrating the complicated operations of droplet generation, cultivation, detection, splitting, fusion and sorting, we design a miniaturized, fully automated and high-throughput microbial microdroplet culture system (MMC). The MMC can be widely used in microbial growth curve test, laboratory adaptive evolution, single factor and multi-level analysis of microbial culture, metabolite detection and so on, and provide a powerful instrument platform for customized microbial evolution and screening aiming at efficient strain engineering.

PMID:33783163 | DOI:10.13345/j.cjb.200667

Sheng Wu Gong Cheng Xue Bao. 2021 Mar 25;37(3):980-990. doi: 10.13345/j.cjb.200613.

ABSTRACT

Aspergillus niger is a vital industrial workhouse widely used for the production of organic acids and industrial enzymes. This fungus is a crucial cell factory due to its innate tolerance to a diverse range of abiotic conditions, high production titres, robust growth during industrial scale fermentation, and status as a generally recognized as safe (GRAS) organism. Rapid development of synthetic biology and systems biology not only offer powerful approaches to unveil the molecular mechanisms of A. niger productivity, but also provide more new strategies to construct and optimize the A. niger cell factory. As a new generation of genome editing technology, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated (Cas) system brings a revolutionary breakthrough in targeted genome modification for A. niger. In this review, we focus on current advances to the CRISPR/Cas genome editing toolbox, its application on gene modification and gene expression regulation in this fungal. Moreover, the future directions of CRISPR/Cas genome editing in A. niger are highlighted.

PMID:33783162 | DOI:10.13345/j.cjb.200613

Sheng Wu Gong Cheng Xue Bao. 2021 Mar 25;37(3):966-979. doi: 10.13345/j.cjb.200645.

ABSTRACT

Methylotrophic yeasts are considered as promising cell factories for bio-manufacturing due to their several advantages such as tolerance to low pH and high temperature. In particular, their methanol utilization ability may help to establish a methanol biotransformation process, which will expand the substrate resource for bio-refinery and the product portfolio from methanol. This review summarize current progress on engineering methylotrophic yeasts for production of proteins and chemicals, and compare the strengths and weaknesses with the model yeast Saccharomyces cerevisiae. The challenges and possible solutions in metabolic engineering of methylotrophic yeasts are also discussed. With the developing efficient genetic tools and systems biology, the methylotrophic yeasts should play more important roles in future green bio-manufacturing.

PMID:33783161 | DOI:10.13345/j.cjb.200645

Sheng Wu Gong Cheng Xue Bao. 2021 Mar 25;37(3):846-859. doi: 10.13345/j.cjb.200642.

ABSTRACT

Microbial oils are potential resources of fuels and food oils in the future. In recent years, with the rapid development of systems biology technology, understanding the physiological metabolism and lipid accumulation characteristics of oleaginous microorganisms from a global perspective has become a research focus. As an important tool for systems biology research, omics technology has been widely used to reveal the mechanism of high-efficiency production of oils by oleaginous microorganisms. This provides a basis for rational genetic modification and fermentation process control of oleaginous microorganisms. In this article, we summarize the application of omics technology in oleaginous microorganisms, introduced the commonly used sample pre-processing and data analysis methods for omics analysis of oleaginous microorganisms, reviewe the researches for revealing the mechanism of efficient lipid production by oleaginous microorganisms based on omics technologies including genomics, transcriptomics, proteomics (modification) and metabolomics (lipidomics), as well as mathematical models based on omics data. The future development and application of omics technology for microbial oil production are also proposed.

PMID:33783154 | DOI:10.13345/j.cjb.200642