Minimalist Adjuvant-Free Nano-Vaccine Based on Antigen Self-Assembled Amyloid-Like Fibrils to Induce Potent Immune Response.

The development of cancer vaccines is at the forefront of cancer immunotherapy. Most existing strategies to induce an efficient anti-tumor immune response rely on molecular adjuvants and the incorporation of complex synthetic vectors into vaccine formulations. In contrast, this study introduces a one-step engineering technique to assemble the model antigen, Ovalbumin (OVA), into amyloid aggregates, leveraging biomimetic folding and aggregation to create non-fibrillar OVA globular aggregates and OVA amyloid-like fibrils as single-component, adjuvant-free vaccines.

Cytokinetic engineering enhances the secretory production of recombinant human lysozyme in Komagataella phaffii.

Background: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast.

HOT-GAN: Hilbert Optimal Transport for Generative Adversarial Network.

Generative adversarial network (GAN) has achieved remarkable success in generating high-quality synthetic data by learning the underlying distributions of target data. Recent efforts have been devoted to utilizing optimal transport (OT) to tackle the gradient vanishing and instability issues in GAN. They use the Wasserstein distance as a metric to measure the discrepancy between the generator distribution and the real data distribution.

The roles of SARP family regulators involved in secondary metabolism in .

species are best known for their ability to produce abundant secondary metabolites with versatile bioactivities and industrial importance. These metabolites are usually biosynthesized through metabolic pathways encoded by cluster-situated genes. These genes are also known as biosynthetic gene clusters (BGCs) of secondary metabolites.

An atypical two-component system, AtcR/AtcK, simultaneously regulates the biosynthesis of multiple secondary metabolites in .

is an industrial producer of milbemycins, which are important anthelmintic and insecticidal agents. Two-component systems (TCSs), which are typically situated in the same operon and are composed of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in . Here, an atypical TCS, AtcR/AtcK, in which the encoding genes (sbi_06838/sbi_06839) are organized in a head-to-head pair, was demonstrated to be indispensable for the biosynthesis of multiple secondary metabolites in .

Enhancement of milbemycins production by phosphopantetheinyl transferase and regulatory pathway engineering in Streptomyces bingchenggensis.

Milbemycins (MILs), a group of 16-membered insecticidal macrocylic lactones, are widely used as the biological pesticide and the precursors of semi-synthetic veterinary drugs. Polyketide synthases (PKSs), which require phosphopantetheinyl transferases (PPTases) to activate their ACP domains from apo forms to holo forms, catalyze the backbone biosynthesis of MILs. Here we found there was a complex phosphopantetheinylation network mediated by five putative PPTases in Streptomyces bingchenggensis.

Rationally Improving Doramectin Production in Industrial Strains.

Avermectins (AVMs), a family of 16-membered macrocyclic macrolides produced by , have been the most successful microbial natural antiparasitic agents in recent decades. Doramectin, an AVM derivative produced by mutants through cyclohexanecarboxylic acid (CHC) feeding, was commercialized as a veterinary antiparasitic drug by Pfizer Inc. Our previous results show that the production of avermectin and actinorhodin was affected by several other polyketide biosynthetic gene clusters in and , respectively.

Leveraging employee online reviews for improving hotel competitiveness in the great resignation.

The Great Resignation has brought significant challenges to the recovery of the hospitality industry from the depression caused by the coronavirus pandemic (COVID-19). Prior studies have revealed that the leading cause of the Great Resignation is negative employee experience. However, few empirical studies have been conducted to obtain deep insights into the negative experiences of hospitality employees.

Elucidation of the ferrichrome siderophore biosynthetic pathway in albomycin-producing Streptomyces sp. ATCC 700974.

Sideromycins are a unique subset of siderophores comprising of a siderophore conjugated to an antimicrobial agent. The "Trojan horse" antibiotic albomycins are unique sideromycins consisting of a ferrichrome-type siderophore conjugated to a peptidyl nucleoside antibiotic. They exhibit potent antibacterial activities against many model bacteria and a number of clinical pathogens.

Roles of LuxR-family regulators in the biosynthesis of secondary metabolites in Actinobacteria.

Actinobacteria are well-known Gram-positive bacteria that produce approximately two-thirds of microbial bioactive natural products (NPs) through secondary metabolism. Usually, genes involved in the biosynthesis of NPs in actinobacteria are clustered, and their expression is regulated by an elaborate and stringent regulatory network formed by diverse regulators. These regulators can be classified into more than 50 superfamilies/families according to conserved amino acid sequences and biological functions.

Genome sequencing of Colletotrichum gloeosporioides ES026 reveals plausible pathway of HupA.

Background: Colletotrichum gloeosporioides ES026, isolated as an endophytic fungal strain, was found to produce the important medicinal compound HuperzineA (HupA). In a genetic context, ES026 showed potential in elucidating the biosynthetic pathway of HupA.

Methods And Results: The ES026 strain was sequenced using de-novo Illumina sequencing methods in this study.

MilR3, a unique SARP family pleiotropic regulator in Streptomyces bingchenggensis.

Streptomyces bingchenggensis is the main industrial producer of milbemycins, which are a group of 16-membered macrocylic lactones with excellent insecticidal activities. In the past several decades, scientists have made great efforts to solve its low productivity. However, a lack of understanding of the regulatory network of milbemycin biosynthesis limited the development of high-producing strains using a regulatory rewiring strategy.

An Improved CenterNet Model for Insulator Defect Detection Using Aerial Imagery.

For the issue of low accuracy and poor real-time performance of insulator and defect detection by an unmanned aerial vehicle (UAV) in the process of power inspection, an insulator detection model MobileNet_CenterNet was proposed in this study. First, the lightweight network MobileNet V1 was used to replace the feature extraction network Resnet-50 of the original model, aiming to ensure the detection accuracy of the model while speeding up its detection speed. Second, a spatial and channel attention mechanism convolutional block attention module (CBAM) was introduced in CenterNet, aiming to improve the prediction accuracy of small target insulator position information.

Recent advances in the research of milbemycin biosynthesis and regulation as well as strategies for strain improvement.

Milbemycins, a group of 16-membered macrocylic lactones with excellent acaricidal, insecticidal and anthelmintic activities, can be produced by several Streptomyces species. For the reason that they have low toxicity in mammals, milbemycins and their derivatives are widely used in agricultural, medical and veterinary industries. Streptomyces bingchenggensis, one of milbemycin-producing strains, has been sequenced and intensively investigated in the past decades.

CRISPR-Cas12-based nucleic acids detection systems.

Because of the outstanding contribution in genome editing, CRISPR has undoubtedly become the most popular technology around the world and two pioneers are awarded the Nobel Prize in Chemistry this year. Besides, along with the discovery of nonspecific trans-cleavage activities of several Cas proteins such as Cas12 and Cas13, many CRISPR-based molecular diagnostic systems have been successfully created, showing advantages in sensitivity, specificity and operation convenience. Among them, systems with Cas12, which targets DNA and trans-cleaves single-stranded DNA probes, are both simple and highly efficient.

Corrigendum: The Application of Regulatory Cascades in : Yield Enhancement and Metabolite Mining.

[This corrects the article DOI: 10.3389/fmicb.2020.

The Application of Regulatory Cascades in : Yield Enhancement and Metabolite Mining.

is taken as an important resource for producing the most abundant antibiotics and other bio-active natural products, which have been widely used in pharmaceutical and agricultural areas. Usually they are biosynthesized through secondary metabolic pathways encoded by cluster situated genes. And these gene clusters are stringently regulated by interweaved transcriptional regulatory cascades.

The regulatory cascades of antibiotic production in Streptomyces.

Streptomyces is famous for its capability to produce the most abundant antibiotics in all kingdoms. All Streptomyces antibiotics are natural products, whose biosynthesis from the so-called gene clusters are elaborately regulated by pyramidal transcriptional regulatory cascades. In the past decades, scientists have striven to unveil the regulatory mechanisms involved in antibiotic production in Streptomyces.

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces.

The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide.

A New Medium for Improving Spinosad Production by Saccharopolyspora spinosa.

Background: Spinosad (a mixture of spinosyns A and D) is a unique natural pesticide produced by Saccharopolyspora spinosa. With regard to attempts to improve S. spinosa by classical mutagenesis, we propose that the bottleneck of screening out high-spinosad-production strains is probably caused by the fermentation media.

Characterization of the chromosomal integration of Saccharopolyspora plasmid pCM32 and its application to improve production of spinosyn in Saccharopolyspora spinosa.

Saccharopolyspora spinosa produces tetra-cyclic macrolide spinosyns, a group of highly efficient pesticidal agents. However, this species lacks efficient vectors for genetic manipulation. In this study, the circular plasmid pCM32 was newly isolated from Saccharopolyspora endophytica YIM 61095.

MEGA (Multiple Essential Genes Assembling) deletion and replacement method for genome reduction in Escherichia coli.

Top-down reduction of the bacterial genome to construct desired chassis cells is important for synthetic biology. However, the current progress in the field of genome reduction is greatly hindered by indispensable life-essential genes that are interspersed throughout the chromosomal loci. Here, we described a new method designated as "MEGA (Multiple Essential Genes Assembling) deletion and replacement" that functions by assembling multiple essential genes in an E.

New aminocoumarins from the rare actinomycete Catenulispora acidiphila DSM 44928: identification, structure elucidation, and heterologous production.

Genome mining led to the discovery of a novel aminocoumarin gene cluster in the rare actinomycete Catenulispora acidiphila DSM 44928. Sequence analysis revealed the presence of genes putatively involved in export/resistance, regulation, and biosynthesis of the aminocoumarin moiety and its halogenation, as well as several genes with so far unknown function. Two new aminocoumarins, cacibiocin A and B, were identified in the culture broth of C.