According to Darwin’s theory, endless evolution leads to a revolution. One such example is the Clustered Regularly Interspaced Palindromic Repeats (CRISPR)–Cas system, an adaptive immunity system in most archaea and many bacteria. Gene editing technology possesses a crucial potential to dramatically impact miscellaneous areas of life, and CRISPR–Cas represents the most suitable strategy. The system has ignited a revolution in the field of genetic engineering. The ease, precision, affordability of this system is akin to a Midas touch for researchers editing genomes. Undoubtedly, the applications of this system are endless. The CRISPR–Cas system is extensively employed in the treatment of infectious and genetic diseases, in metabolic disorders, in curing cancer, in developing sustainable methods for fuel production and chemicals, in improving the quality and quantity of food crops, and thus in catering to global food demands. Future applications of CRISPR–Cas will provide benefits for everyone and will save countless lives. The technology is evolving rapidly; therefore, an overview of continuous improvement is important. In this review, we aim to elucidate the current state of the CRISPR–Cas revolution in a tailor-made format from its discovery to exciting breakthroughs at the application level and further upcoming trends related to opportunities and challenges including ethical concerns.

Novel CRISPR-Cas Systems: An Updated Review of the Current Achievements, Applications, and Future Research Perspectives.

https://pubs.rsc.org/en/content/articlepdf/2021/NP/D1NP00035G

Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis.

Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis

Brazilian economy is one of the most important agriculture-based economies in the world, producing coffee, sugarcane, soybean, cassava, fruits and other commodities. This production is responsible for the generation of enormous amounts of daily residues, such as cassava and sugarcane bagasses, rice husk, and coffee peel. These residues are rich sources for renewable energy and can be used as substrates for industrial interest products. Microorganisms are useful biofactories, capable of producing important primary and secondary metabolites, including alcohol, enzymes, antibiotics, pigments, and many other molecules. The production of pigments was reported in bacteria, filamentous fungi, yeasts, and algae. These natural microbial pigments are very promising because synthetic colorants present a long history of allergies and toxicity. In addition, many natural pigments present other biological activities, such as antioxidant and antimicrobial that are interesting for industrial applications. The use of inexpensive substrates for the production of these metabolites is very attractive, considering that agro-industrial residues are generated in high amounts and usually are a problem to the industry. Therefore, in this article we review the production of microbial pigments using agro-industrial residues during this decade (2010-2020), considering both submerged and solid state fermentations, wild-type and genetically modified microorganisms, laboratorial to large-scale bioprocesses, and other possible biological activities related to these pigments.

/pdf/agro-industrial-residues-eco-friendly-and-inexpensive-1ccavbpxog.pdf

Agro-Industrial Residues: Eco-Friendly and Inexpensive Substrates for Microbial Pigments Production

Filamentous fungi for future functional food and feed.

Mycotoxin contamination causes disease and death in both humans and animals. Monascus Red, produced by Monascus purpureus, is used as a food colorant. However, its application is limited by contami...

A dual-plasmid CRISPR/Cas system for mycotoxin elimination in polykaryotic industrial fungi

Quinolactacins are novel fungal alkaloids that feature a quinolone-γ-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Herein, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone-γ-lactam structure. We reveal an unusual β-keto acid (N-methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite l-kynurenine via methylation, oxidative decarboxylation, and amide hydrolysis reactions. In vitro assays reveal two single-module non-ribosomal peptide synthetases (NRPs) that incorporate the β-keto acid and l-isoleucine, followed by Dieckmann condensation, to form the quinolone-γ-lactam. Notably, the bioconversion from l-kynurenine to the β-keto acid is a unique strategy employed by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expanding the paradigm for the biosynthesis of quinolone-γ-lactam natural products via Dieckmann condensation.

Quinolactacin Biosynthesis Involves Non‐Ribosomal‐Peptide‐Synthetase‐Catalyzed Dieckmann Condensation to Form the Quinolone‐γ‐lactam Hybrid

Quinolactacin Biosynthesis Involves NRPSs Catalyzed Dieckmann Condensation to Form the Quinolone‐γ‐lactam Hybrid

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Tianqi Pingchan Granule (TPG) is a clinically effective formula of traditional Chinese medicine to treat PD. However, the therapeutic effect and underlying mechanisms of TPG in PD remain unclear. Based on network pharmacology, the corresponding targets of TPG were identified using the Traditional Chinese Medicine Database and Analysis Platform Database. Differentially expressed genes in PD were obtained from the Therapeutic Target Database, Online Mendelian Inheritance in Man, GeneCards, and DrugBank databases. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to the pathogenesis of PD were integrated manually. Furthermore, in vivo studies were carried out based on network pharmacology. The gut microbiota, peripheral inflammatory cytokines, and glia-mediated neuroinflammation in substantia nigra were evaluated. A total of 99 target genes were intersected between targets of TPG and deferentially expressed genes in PD. The PPI network analysis indicated the proinflammatory cytokine as essential targets. GO and KEGG analyses indicated that inflammatory response and its related signaling pathways were closely associated with TPG-mediated PD treatment. In vivo studies revealed that class Negativicutes and order Selenomonadales decreased, whereas class Mollicutes, order Enterobacteriales, and Mycoplasmatales increased in fecal samples of PD rats via 16S rRNA sequence analysis. Furthermore, the function prediction methods purposely revealed that TPG therapy may be involved in flavonoid biosynthesis, which have anti-inflammatory properties. In addition, in vivo studies revealed that TPG exposure was found to not only attenuate the production of peripheral inflammatory cytokines but also inhibit the activation of microglia and astrocytes in substantia nigra of PD rats. Through network pharmacology and in vivo experiment-combined approach, the mechanisms of TPG in the treatment of PD were revealed, and the role of TPG in the regulation of gut microbiota and inflammatory response was confirmed.

Network Pharmacology and Absolute Bacterial Quantification-Combined Approach to Explore the Mechanism of Tianqi Pingchan Granule Against 6-OHDA-Induced Parkinson’s Disease in Rats

A chemo- and enantioselective protocol for the N-alkylation of indoles with imines was developed. This process was catalyzed by a BINOL-derived phosphoric acid catalyst to give the corresponding acyclic aminals of indoles in 46–99% yields with 70–98% ee. The application of this method for the “late-stage” functionalization of a bioactive compound was performed with high efficency. The products showed good stability and enabled many further transformations. 

Shuyuan Yang

Papers

A dual-plasmid CRISPR/Cas system for mycotoxin elimination in polykaryotic industrial fungi

Quinolactacin Biosynthesis Involves Non‐Ribosomal‐Peptide‐Synthetase‐Catalyzed Dieckmann Condensation to Form the Quinolone‐γ‐lactam Hybrid

Quinolactacin Biosynthesis Involves NRPSs Catalyzed Dieckmann Condensation to Form the Quinolone‐γ‐lactam Hybrid

Network Pharmacology and Absolute Bacterial Quantification-Combined Approach to Explore the Mechanism of Tianqi Pingchan Granule Against 6-OHDA-Induced Parkinson’s Disease in Rats

Chiral Phosphoric Acid‐Catalyzed Chemo‐ and Enantioselective N‐Alkylation of Indoles with Imines