Biosynthesis Research Articles

NRPS-like Gene LYS2 Contributed to the Biosynthesis of Cyclo(Pro-Val) in a Multistress-Tolerant Aromatic Probiotic, Meyerozyma guilliermondii GXDK6.

Cyclo(Pro-Val) is a diketopiperazine (DKP) found widespread in marine microbes and resulting food products. With new bioactivities of cyclo(Pro-Val) being continually discovered, its potential applications in agriculture and food are becoming more evident, highlighting the need for efficient and practical methods to produce these compounds. However, the biosynthesis mechanisms of cyclo(Pro-Val), particularly in probiotics, remain unclear, and the functional identification of nonribosomal peptide synthases (NRPS) is still limited. This study presents a new efficient cyclo(Pro-Val) production system using the marine probiotic Meyerozyma guilliermondii (M. guilliermondii) GXDK6 as a chassis cell. We further characterized an NRPS-like gene, LYS2, which spans 3825 bp and encodes an l-2-amino-hexanedioic acid reductase (Lys2p) consisting of 1274 amino acids. A novel macrocyclization mechanism was revealed involving the peptide N-terminal and C-terminal imines mediated by Lys2p through nucleophilic reactions. Overexpressing LYS2 in GXDK6 resulted in a 45.5% increase in cyclo(Pro-Val) production, while knockout LYS2 completely halted its synthesis. This study revealed a novel metabolic regulatory pathway and biosynthetic mechanism for cyclo(Pro-Val) in marine yeast M. guilliermondii GXDK6. Refactoring the biosynthetic pathway in yeast through LYS2 provides an alternative approach for producing cyclo(Pro-Val).

Complete Epoxy Phosphonate Conversion to Dimethyl (1E)-3-Hydroxyprop-1-Enylphosphonate with Photobiocatalysts’ Assistance

Phosphonates derivatives are compounds of interests and are applied as drugs of, e.g., antibacterial antiviral activities, connected with their inhibitory activity towards different enzymes, which is related to the configuration of particular compound isomers. The biological synthesis of such molecules is the method of choice and can be carried out using enzymes or whole cells from organisms. Photobiocatalysts employed in the bioconversion of epoxymethyl dimethyl phosphonate are able to convert this substrate into a pure geometric isomer of the unsaturated product, dimethyl (1E)-3-hydroxyprop-1-enylphosphonate, which is a rare and expensive compound of high added value. Six different strains were screened towards dimethyl epoxy phosphonate and in the case of Synechococcus bigranulatus, over 99% conversion was achieved. The product structure was confirmed with Mass Spectroscopy (MS); 1H, 13C, 31P, and 2D Nuclear Magnetic Resonance (NMR); and Infrared Spectroscopy (IR).

Biological Synthesis of Silver Nanoparticles Using Klebsiella pneumoniae (ON640793) and Assessment of Its Antibacterial, Larvicidal and Biotoxicity Efficiency

Biological Synthesis of Silver Nanoparticles Using Klebsiella pneumoniae (ON640793) and Assessment of Its Antibacterial, Larvicidal and Biotoxicity Efficiency

Genome-Wide Identification and Characterization of OSC Gene Family in Gynostemma pentaphyllum (Cucurbitaceae)

Gynostemma pentaphyllum is a traditional Chinese medicinal plant of considerable application value and commercial potential, primarily due to its production of various bioactive compounds, particularly dammarane-type triterpenoid saponins that are structurally analogous to ginsenosides. Oxidosqualene cyclase (OSC), a pivotal enzyme in the biosynthesis of triterpenoid metabolites in plants, catalyzes the conversion of oxidosqualene into triterpenoid precursors, which are essential components of the secondary metabolites found in G. pentaphyllum. To elucidate the role of OSC gene family members in the synthesis of gypenosides within G. pentaphyllum, this study undertook a comprehensive genome-wide identification and characterization of OSC genes within G. pentaphyllum and compared their expression levels across populations distributed over different geographical regions by both transcriptome sequencing and qRT-PCR experimental validation. The results identified a total of 11 members of the OSC gene family within the genome of G. pentaphyllum. These genes encode proteins ranging from 356 to 767 amino acids, exhibiting minor variations in their physicochemical properties, and are localized in peroxisomes, cytoplasm, plasma membranes, and lysosomes. All GpOSCs contain highly conserved DCTAE and QW sequences that are characteristic of the OSC gene family. A phylogenetic analysis categorized the GpOSCs into four distinct subfamilies. A cis-element analysis of the GpOSC promoters revealed a substantial number of abiotic stress-related elements, indicating that these genes may respond to drought conditions, low temperatures, and anaerobic environments, thus potentially contributing to the stress resistance observed in G. pentaphyllum. Expression analyses across different G. pentaphyllum populations demonstrated significant variability in OSC gene expression among geographically diverse samples of G. pentaphyllum, likely attributable to genetic variation or external factors such as environmental conditions and soil composition. These differences may lead to the synthesis of various types of gypenosides within geographically distinct G. pentaphyllum populations. The findings from this study enhance our understanding of both the evolutionary history of the OSC gene family in G. pentaphyllum and the biosynthetic mechanisms underlying triterpenoid compounds. This knowledge is essential for investigating molecular mechanisms involved in forming dammarane-type triterpenoid saponins as well as comprehending geographical variations within G. pentaphyllum populations. Furthermore, this research lays a foundation for employing plant genetic engineering techniques aimed at increasing gypenoside content.

Green Synthesis of Zinc Oxide Nanoparticles: Preparation, Characterization, and Biomedical Applications - A Review.

Over the last decade, biomedical nanomaterials have garnered significant attention due to their remarkable biological properties and diverse applications in biomedicine. Metal oxide nanoparticles (NPs) are particularly notable for their wide range of medicinal uses, including antibacterial, anticancer, biosensing, cell imaging, and drug/gene delivery. Among these, zinc oxide (ZnO) NPs stand out for their versatility and effectiveness. Recently, ZnO NPs have become a primary material in various sectors, such as pharmaceutical, cosmetic, antimicrobials, construction, textile, and automotive industries. ZnO NPs can generate reactive oxygen species and induce cellular apoptosis, thus underpinning their potent anticancer and antibacterial properties. To meet the growing demand, numerous synthetic approaches have been developed to produce ZnO NPs. However, traditional manufacturing processes often involve significant economic and environmental costs, prompting a search for more sustainable alternatives. Intriguingly, biological synthesis methods utilizing plants, plant extracts, or microorganisms have emerged as ideal for producing ZnO NPs. These green production techniques offer numerous medicinal, economic, environmental, and health benefits. This review highlights the latest advancements in the green synthesis of ZnO NPs and their biomedical applications, showcasing their potential to revolutionize the field with eco-friendly and cost-effective solutions.

Recent advances of natural product pesticide milbemycins from Streptomyces

AbstractMilbemycins are a group of 16‐membered macrolides produced by the soil‐dwelling filamentous bacteria Streptomyces. Renowned for their potent acaricidal and insecticidal properties, combined with low toxicity, milbemycins are recognized as eco‐friendly biopesticides, vital for pest control and sustainable agricultural development. Over several decades, milbemycins have been extensively investigated, achieving significant progress, including advancements in their biological activities (such as insecticidal mechanisms and toxicity studies), biosynthetic and regulatory mechanisms, high‐yield strain engineering strategies, and the development of milbemycin‐derived commercial products for agricultural applications. This review discusses recent advances, current limitations, and ongoing and emerging efforts to overcome the limitations of milbemycin research. Finally, future research directions are outlined for the development of superior milbemycin‐producing cell factories to facilitate widespread application in the agricultural field.

Discovery of new insecticidal cyclic hexapeptides from Fusarium tricinctum HM76 and their biosynthesis

Fungi often produce a variety of natural products that are toxic to insects, making them an important resource for the discovery of new insecticides. In previous screenings, the crude extract from the wheat pathogen Fusarium tricinctum HM76 exhibited notable insecticidal activity. A chemical investigation of the extract led to the isolation of six undescribed cyclic hexapeptides Futrines (1–6). Their structures were determined through elucidation of NMR and HRESIMS data, as well as chiral HPLC analysis. All the isolated compounds were tested for insecticidal activities against Aphis citricola Van der Goo and Tetranychus cinnabarinus Boisduval. Notably, compounds 2 and 6 demonstrated significant insecticidal activities against T. cinnabarinus and A. citricola, with LC50 and LD50 values of 0.212 mg/mL and 2.230 ng/nymph, respectively. Additionally, the biosynthetic gene cluster responsible for the production of futrines was identified through gene knockout, offering insight into their biosynthetic mechanism. These findings highlight the potential of these cyclic hexapeptides as promising candidates for new insecticide development.

Preliminary exploration of the musk biosynthetic mechanism by transcriptomic sequencing in muskrats

Musk, secreted by adult male forest musk deer, is a kind of precious Chinese traditional medicine for treating cardiovascular, cerebrovascular and neurogenic diseases. However, a lack of knowledge on musk biosynthetic mechanism and limited musk deer population have seriously hindered the development of the musk industry. Fortunately, given that muskrat musk has similar constituents and pharmacological action with deer musk, muskrat is an ideal model animal for exploring musk biosynthetic mechanism. To explore the biosynthetic mechanism of muskrat musk, in the current study, transcriptomic analysis in the liver, kidney and musk glands of male muskrats between musk secreting and non-musk secreting stages was conducted. The findings indicated that the role of muskrat liver on musk biosynthesis was altering sugar, lipid and amino acid metabolism as well as producing basic resources to support musk glands. Moreover, Tigar, Slc11a2, Gpt, Hmgcr, Slc27a4, and Elovl1 were identified as candidate genes for musk biosynthesis via a remotely controlled process. Expression of the Tigar, Slc11a2, and Gpt genes in the liver are downregulated to support the production of musk in muskrat musk gland. And the Hmgcr, Slc27a4, and Elovl1 genes in the musk gland participate in muskrat musk synthesis by influencing lipid metabolism in the musk secreting period. This study provided novel insights into the musk biosynthetic pathway in muskrat by transcriptomic analysis and preliminarily suggested the remote control of metabolism from the liver to musk gland during musk biosynthesis, which was useful to further understanding the musk biosynthetic process and improve musk production in the future.

Biogenic Nanoparticles as Safer Alternatives for Gastric Ulcers: An Update on Green Synthesis Methods, Toxicity, and Their Efficacy in Controlling Inflammation.

Peptic ulcers, affecting approximately 10% of the global population, can result from factors such as stress, alcohol use, smoking, NSAIDs, Helicobacter pylori infection, and genetic predisposition. Plant-based medicines are gaining recognition for their therapeutic potential, including in the treatment of peptic ulcers. Green chemistry methods for the biological synthesis of nanoparticles (NPs) provide a sustainable alternative to traditional chemical techniques. These nanoparticles, particularly metallic NPs and metal oxides synthesized from plant extracts, offer promising anti-ulcer properties. This review highlights research from 2000 to 2024 on the use of green-synthesized nanoparticles and their role in peptic ulcer treatment, focusing on their therapeutic mechanisms and potential benefits. For this purpose, an electronic search of published research and review articles was conducted in PubMed, Scopus, Science Direct, Cochrane databases, and Google Scholar.

New trends in mycosynthesis of cellulose nanocrystals promoted by gamma irradiation of sugarcane bagasse

AbstractThe biological synthesis of cellulose nanocrystals (CNCs) involves utilizing cellulose-degrading microorganisms or their hydrolytic enzymes as catalysts for the controlled degradation of cellulose, yielding CNCs. Chemical synthesis of CNCs involves acid hydrolysis conducted for 45 min at 45 °C using sulfuric acid (64%). Neurospora intermedia (Assiut University Mycological Center (AUMC) 14,359), Fusarium verticillioides (AUMC 14360), and Rhizopus oryzae (AUMC 14361) were employed in the preparation of CNCs. Before both chemical and biological treatments, sugarcane bagasse (SCB) was irradiated with doses of 100, 200, and 300 kGy, enhancing the yield of nanocellulose from the cellulosic feedstock. The resultant nanocellulose was initially assessed using UV–Vis spectroscopy, and the characterization was further refined through Dynamic Light Scattering analysis to delineate particle size distribution within the nanoscale and to evaluate stability. CNCs and chemically purified cellulose (CPC) displayed analogous Fourier Transform Infrared Spectroscopy but were markedly different from SCB. X-ray Diffraction patterns revealed a notably higher crystallinity of cellulose in nanocellulose, with larger crystallite dimensions compared to CPC and SCB. Transmission Electron Microscope investigations elucidated the morphology of the synthesized nanoparticles. In summary, the selection of F. verticillioides for nanocellulose production represents a promising and sustainable approach that combines effectiveness, environmental friendliness, and cost-efficiency in the synthesis of this valuable nanomaterial. Graphical abstract

Screening the silver nanoparticle synthesis potential of endophytic fungi with special reference to their antibacterial activity

Nanobiotechnology is the innovative field of science which involves biological synthesis, characterization and application of numerous nanoparticles. The present study was planned to explore potential of endophytic fungi for eco-friendly synthesis of silver nanoparticles with antibacterial activity. In this study 8 endophytic fungal isolates were obtained from different parts of medicinal plants. These isolates were identified belonging to different genera namely, Penicillium, Aspergillus, Alternaria etc. All endophytic fungi were subjected to extra cellular biosynthesis of silver nanoparticles. Out of these Penicillium sp.,Aspergillus sp., Alternaria sp., isolated from healthy plant parts of Aegle marmelos, Dalbergia sissoo and Lantana camara respectively, gave positive results. The antibacterial activities of these nanoparticles were determined against some pathogenic bacteria by Agar Well Diffusion assay. During which it was found that the silver nanoparticles sample exhibiting highest antibacterial potential was characterized by UV-Visible Spectroscopy, Dynamic Light Scattering (DLS), Zeta Potential analysis and Transmission Electron Microscopy. UV-Visible spectroscopy analysis gave surface plasmone resonance peak alternatively 416nm, 444nm and420nm.The average size range of silver nanoparticles as determined via, dynamic light scattering analysis is: 126nm, 88nm, 141nm. The Zeta potential of three samples as determined by zeta sizer showed a high negative surface charge on them which confers stability to them. The zeta potentials of these particles are: -19.1 mV, -22.0 mV, -16.2 mV. Silver nanoparticles produced by endophytic fungi displays considerable antibacterial agent and hence the study would prove to provide novel antibacterial agents.

Industrial–scale production of various bio–commodities by engineered microbial cell factories: Strategies of engineering in microbial robustness

The utilization of renewable, non–edible biomass for synthesis of valuable bio–products including bio–fuels, bio-chemicals and bio–polymeric materials, in an environmentally sustainable manner is crucial for addressing the urgent environmental challenges caused by our substantial dependence on fossil fuel resources. In this context, engineered microbial cell factories (MCFs), which are the modified microorganisms, have gained attention and provide biosynthetically optimized pathways for the production of desired bio–commodities using renewable carbon sources. Biosynthetic routes for the production of such bio–commodities can be categorized into three groups based on the chosen microbial host for genetic modification: native, non–native, and artificial pathways. Engineered MCFs are increasingly essential in the pharmaceutical, food, and bio–chemical industries and are being developed to address the growing world population and socioeconomic crisis. Mainly, microorganisms have been utilized in the manufacturing of a range of bio–products including amino acids, carboxylic acids, carotenoids, enzymes, vitamins, plant natural products, biogas, and other biofuels. Furthermore, the implementation of advanced metabolic engineering and synthetic biology tools & techniques enhances the speed, concentration, and efficiency of commercially important substances by modifying the metabolism, carbon–energy balance and eliminating an undesired ATP sink, physiology, and stress response. All these has resulted in rapid growth of industrial biotechnology for production of several bio–commodities. Further, the scale and numbers of bio–commodities is increasing with time. This review summarizes the design of MFCs, selection of microbial strains, metabolic pathways, engineered MCFs for industrial–scale applications, strategies for engineering microbial robustness, commercial restrictions, and their future prospects.

Molecular mechanisms underlying floral fragrance in Camellia japonica 'High Fragrance': a time-course assessment.

Camellia japonica 'High Fragrance' is a camellia hybrid known for its unique and intense floral scent. The current understanding of the dynamic changes in its fragrance and the underlying mechanisms are still limited. This study employed a combination of metabolomic and transcriptomic approaches to reveal the characteristics of the metabolites involved in the remarkable fragrance of this camellia and their biosynthetic mechanisms along three flower developmental stages (flower bud, initial bloom, and full bloom). Among the 349 detected volatile organic compounds (VOCs), the majority were terpenes (57, 16.33%) and esters (53, 15.19%). Of these, 136 VOCs exhibited differential accumulation over time. Transcriptomic data from floral organs at different flowering stages identified 56,303 genes, with 13,793 showing significant differential expression. KEGG enrichment analysis revealed 57, 91, and 33 candidate differential genes related to the biosynthesis of terpenes, phenylpropanoids, and fatty acid derivatives, respectively. This indicates that terpenes, esters, and their related synthetic genes might play a crucial role in the formation of 'High Fragrance' characteristics. During the entire flowering process, the majority of genes exhibited an elevated expression pattern, which correlated with the progressive accumulation of VOCs. Interestingly, the expression patterns of the differentially expressed genes in the mevalonate (MVA) and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathways, associated with terpene synthesis, showed opposite trends. A transcriptional-metabolic regulatory network linking terpenoid compounds, related synthetic enzymes, and potential transcription factors could be outlined for 'High Fragrance' camellia, thus providing a theoretical basis for further exploring these events and breeding more fragrant camellias.

Modifications of Prenyl Side Chains in Natural Product Biosynthesis.

In recent years, there has been a growing interest in understanding the enzymatic machinery responsible for the modifications of prenyl side chains and elucidating their roles in natural product biosynthesis. This interest stems from the pivotal role such modifications play in shaping the structural and functional diversity of natural products, as well as from their potential applications to synthetic biology and drug discovery. In addition to contributing to the diversity and complexity of natural products, unique modifications of prenyl side chains are represented by several novel biosynthetic mechanisms. Representative unique examples of epoxidation, dehydrogenation, oxidation of methyl groups to carboxyl groups, unusual C-C bond cleavage and oxidative cyclization are summarized and discussed. By revealing the intriguing chemistry and enzymology behind these transformations, this comprehensive and comparative review will guide future efforts in the discovery, characterization and application of modifications of prenyl side chains in natural product biosynthesis.

Modifications of Prenyl Side Chains in Natural Product Biosynthesis

AbstractIn recent years, there has been a growing interest in understanding the enzymatic machinery responsible for the modifications of prenyl side chains and elucidating their roles in natural product biosynthesis. This interest stems from the pivotal role such modifications play in shaping the structural and functional diversity of natural products, as well as from their potential applications to synthetic biology and drug discovery. In addition to contributing to the diversity and complexity of natural products, unique modifications of prenyl side chains are represented by several novel biosynthetic mechanisms. Representative unique examples of epoxidation, dehydrogenation, oxidation of methyl groups to carboxyl groups, unusual C−C bond cleavage and oxidative cyclization are summarized and discussed. By revealing the intriguing chemistry and enzymology behind these transformations, this comprehensive and comparative review will guide future efforts in the discovery, characterization and application of modifications of prenyl side chains in natural product biosynthesis.

Toward Sustainable Utilization and Production of Tartaric Acid.

Global efforts toward establishing a circular carbon economy have guided research interests towards exploring renewable technologies that can replace environmentally harmful fossil fuel-based production routes. In this context, sugar-based bio-derived substrates have been identified as renewable molecules for future implementation in chemical industries. Tartaric acid, a special C4 bio-compound with two hydroxyl and carboxylic groups in the structure, displays great potential for the food, polymer, and pharmaceutical industries due to its unique biological reactivity and performance-enhancing properties. To this point, there has yet to be a comprehensive literature review and perspective on the applications and synthesis of tartaric acid. As such, we have conducted a detailed and thorough outlook and discussion in terms of biological activity, organic synthesis, catalysis, structural characterization and synthetic routes. Lastly, we provide a critical discussion on the applications and synthesis of tartaric acid to give our insights into developing sustainable chemical technologies for the future.

Retinol (Vitamin A) and Its Derivatives: Synthesis and Applications

This paper systematically reviews the synthesis methods of retinol (Vitamin A) and its derivatives, along with their applications in skincare and pharmaceuticals. By examining traditional chemical synthesis pathways such as the Roche, BASF, and Rhone-Poulenc routes, as well as modern biological synthesis pathways, the paper highlights the advantages and limitations of each method, particularly in terms of improving synthesis efficiency, reducing production costs, and minimizing environmental impact. The paper also analyzes the application of retinol derivatives in skincare, including their roles in anti-aging, skin barrier repair, skin whitening, and even tone. Additionally, the paper discusses methods to enhance the stability and bioactivity of retinol. Future directions include further innovation in synthesis techniques, the development of new derivatives, and new pharmaceutical applications of retinol. The paper concludes that retinol and its derivatives hold great promise in the beauty and health sectors, though further research is needed to overcome current challenges and promote wider application.

Staggering cytotoxic effects of manganese oxide nanoparticles from Bacillus thuringiensis

The current study describes the biological synthesis of manganese oxide nanoparticles from Bacillus thuringiensis, as well as their characterization, biological activity, and toxicity. Nanoparticles may be synthesized in multiple ways, but the biogenic process is the most environmentally friendly and cost-effective. The optical, structural, and crystalline properties of the nanoparticles were investigated. A distinctive peak at 246 nm with a band gap of 3.7eV indicates manganese oxide nanoparticle production. A strong peak at 563.09 cm−1 indicates Mn-O stretching in Fourier Transform Infrared Spectroscopy analysis. X-ray diffraction revealed that the crystalline grain size of manganese oxide nanoparticles was 11.23 nm. The agglomerated spherical shape is seen in the Scanning Electron Microscope and High-Resolution Transmission Electron Microscope investigations. The presence of manganese was verified by the EDAX. Manganese oxide nanoparticles have a significant zeta potential peak of −23.4 mV. This work explored the biological activity of manganese oxide nanoparticles, including antibacterial, anti-inflammatory, antioxidant, and biofilm inhibition studies. To investigate cytotoxicity, Allium cepa root tips are treated with manganese oxide nanoparticles.

Insights into the Genome of a New Strain Serratia rubidaea XU1 Isolated from Radioactive Soil and its Prodigiosin Production and Antimicrobial Properties.

The genus Serratia is a typical red bacterium involved in prodigiosin synthesis. Here, we report the genome sequence of Serratia rubidaea XU1, which was isolated from radiation-contaminated soil in Xinjiang, China. The genome of XU1 is composed of 4,972,898 base pairs with a GC content of 59.25%. The genome sequence contains 4707 genes and encodes 4573 proteins, 79 tRNAs, and 17 rRNAs. The prodigiosin biosynthesis gene cluster was identified and analyzed, showing a sequence similarity of 85.55-96.02% with Serratia rubidaea. After optimizing the biosynthesis process, XU1 was able to achieve a maximum titer of 574 units/cell of prodigiosin at a pH of 7.5 and a temperature of 25°C for 36h. Glycerol at 20g/L and beef extract at 5g/L were used as the carbon and nitrogen sources, respectively. Prodigiosin extracted from XU1 demonstrated inhibition of Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. The availability of the sequenced genome of XU1 will be greatly beneficial and contribute to complementary studies on the biosynthetic mechanisms of prodigiosin.

Retraction Note: Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles

Retraction Note: Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles