Biological Factories Research Articles

Unlocking the microbial treasure trove: advances in Streptomyces derived secondary metabolites in the battle against cancer.

Streptomyces is widely recognized as the "biological factory" of specialized metabolites comprising a huge variety of bioactive molecules with diverse chemical properties. The potential of this Gram-positive soil bacteria to produce such diversified secondary metabolites with significant biological properties positions them as an ideal candidate for anticancer drug discovery. Some of the Streptomyces-derived secondary metabolites include siderophores (enterobactin, desferrioxamine), antibiotics (xiakemycin, dinactin) pigments (prodigiosin, melanin), and enzymes (L-methioninase, L-asperginase, cholesterol oxidase) which exhibit a pronounced anticancer effect on both in vitro and in vivo system. These secondary metabolites are endowed with antiproliferative, pro-apoptotic, antimetastatic, and antiangiogenic properties, presenting several promising characteristics that make them suitable candidates in the battle against this deadly disease. In this comprehensive review, we have dived deep and explored their history of discovery, their role as anticancer agents, underlying mechanisms, the approaches for the discovery of anticancer molecules from the secondary metabolites of Streptomyces (isolation of Streptomyces, characterization of bacterial strain, screening for anticancer activity and determination of in vitro and in vivo toxicity, structure-activity relationship studies, clinical translation, and drug development studies). The hurdles and challenges associated with this process and their future prospect were also illustrated. This review highlights the efficacy of Streptomyces as a "microbial treasure island" for novel anticancer agents, which warrants sustained research and exploration in this field to disclose more molecules from Streptomyces that are unidentified and to translate the clinical application of these secondary metabolites for cancer patients.

A one-step route for the conversion of Cd waste into CdS quantum dots by Acidithiobacillus sp. via unique biosynthesis pathways.

Microorganisms serve as biological factories for the synthesis of nanomaterials such as CdS quantum dots. Based on the uniqueness of Acidithiobacillus sp., a one-step route was explored to directly convert cadmium waste into CdS QDs using these bacteria. First, an exhaustive study was conducted to reveal the specific pathways involved in the biosynthesis of CdS QDs. The widely known homologous enzyme, cysteine desulfhydrase, which catalyzes the synthesis of CdS QDs from a cysteine substrate, is also present in Acidithiobacillus sp. and is referred to as the OSH enzyme. The structure of the OSH enzyme was determined through X-ray crystallography. Moreover, we identified two new pathways. One involved the SQR enzyme in Acidithiobacillus sp., which catalyzed the formation of sulfur globules and subsequently catalyzed further reactions with GSH to release H2S; subsequently, a CdS QD biosynthesis pathway was successfully constructed. The other pathway involved extracellular polyphosphate, a bacterial metabolic product, which with the addition of GSH and Cd2+, resulted in the formation of water-soluble fluorescent CdS QDs in the supernatant. Based on the above-described mechanism, after the bioleaching of Cd2+ from cadmium waste by Acidithiobacillus sp., CdS QDs were directly obtained from the bacterial culture supernatants. This work provides important insights into cleaner production and cadmium bioremediation with potential industrial applications.

Study of Different Cultivated Plants Rhizosphere Soil Fungi-Mediated Pectinase: Insights into Production, Optimization, Purification, Biocompatibility, and Application

Microorganisms are preferred as an enzyme source due to their short lifespan, high production rate, affordability, and absence of harmful chemicals in enzymes generated from plant and animal sources. Fungi communities are biological factories for many bioactive compounds such as the important industrial enzyme pectinase. The current study dealt with production, optimization, purification, biocompatibility, and application of fungal pectinase obtained from five plant rhizospheres (banana, jarawa, lemon, tomato, and wheat) at Fayoum Governorate, Egypt. The highest pectinase degrading index (PDI) was scored for FB5, FJ2, and FW1 isolates. Pectinase production was also examined quantitively and the highest output of 1603.67, 1311.22, and 1264.83 U/ml was gained by FB5, FJ1, and FW1 fungal isolates, respectively. The most active pectinase-producing fungi were identified as Aspergillus niveus strain AUMC1624, A. niger strain AUMC16245, and A. brasiliensis strain AUMC16244, respectively. For pectinase production optimization, one factor at a time (OFAT) protocol was applied and revealed that A. niger, A. niveus, and A. brasiliensis reached maximum pectinase levels at 1% pectin after 5, 7, and 7 days, at 40, 45, and 45 °C, respectively. Obtained pectinases were partially purified using ammonium sulfate precipitation (ASP) and organic solvent precipitation (OSP) methods. The highest activity using the ASP method scored at 40–60% saturation with A. niger. The thermostability characterization of A. niger pectinase was reached with relative activities of 61.7, 69.0, 99.9, 91.3, and 90.6% at temperatures ranging between 30 and 70 °C. pH optimized at pH 5–7. The enzyme’s molecular weight was approximately 35 kDa. The GC-mass analysis of pectinase end products included acetic acid ethyl ester, hexadecane carbonsaure methylase, and hexadecenoic acid. The biocompatibility was examined using a human skin cell line (HFb-4) for the first time, with a minimal half concentration (IC50) of 151.86 ± 0.76 U/ml. The biocompatible pectinase was applied as a clothes bioscouring agent with different concentrations of 1893.52 U/ml achieving the highest bioscouring with 20.0%.

Improving trans-cinnamic acid production in a model cyanobacterium.

trans-Cinnamic acid (tCA) is a precursor in the synthesis of many high-value compounds with bio-active qualities useful in applications like medicine, polymers, and cosmetics. Currently tCA is produced by industrial chemical synthesis from fossil fuels or cost-prohibitive isolation from terrestrial plants. Cyanobacteria, a type of photosynthetic bacteria, can be readily engineered to convert sunlight and carbon dioxide into metabolites of interest at relatively high amounts compared to terrestrial plants. The purpose of this study is to advance the industrial and commercial value of cyanobacteria as a biological factory for renewable production of tCA. Production of tCA has previously been demonstrated in the model cyanobacterium Synechocystis sp. PCC 6803 (S. 6803) via expression of non-native phenylalanine ammonia lyase (PAL) from various organisms. This project focuses on developing and characterizing a new high-titer strain of S. 6803 expressing a plant PAL gene controlled by an inducible promoter. We assessed production in shake flasks under constant light, a 12 h:12 h light:dark cycle, and environmental photobioreactors (ePBRs) with a sinusoidal, rapidly fluctuating light environment. Our strain demonstrates a four-fold increase in tCA production to ~500 mg L-1 by 14 days compared to previously reported titers in S. 6803 under shake flask cultivation and a 30-50% improved average tCA production per culture density (60 mg·L-1·OD730 -1) in ePBRs over comparable previously reported culture methods. Our study progresses S. 6803 tCA bioproduction into higher culture volumes, up to 500 mL, while further validating the strength of an inducible system for tCA production in S. 6803.

3D Bioprinting of Microbial-based Living Materials for Advanced Energy and Environmental Applications.

Microorganisms, serving as super biological factories, play a crucial role in the production of desired substances and the remediation of environments. The emergence of 3D bioprinting provides a powerful tool for engineering microorganisms and polymers into living materials with delicate structures, paving the way for expanding functionalities and realizing extraordinary performance. Here, the current advancements in microbial-based 3D-printed living materials are comprehensively discussed from material perspectives, covering various 3D bioprinting techniques, types of microorganisms used, and the key parameters and selection criteria for polymer bioinks. Endeavors on the applications of 3D printed living materials in the fields of energy and environment are then emphasized. Finally, the remaining challenges and future trends in this burgeoning field are highlighted. We hope our perspective will inspire some interesting ideas and accelerate the exploration within this field to reach superior solutions for energy and environment challenges.

The Human Gut Microbiota: A Dynamic Biologic Factory.

The human body constitutes a living environment for trillions of microorganisms, which establish the microbiome and, the largest population among them, reside within the gastrointestinal tract, establishing the gut microbiota. The term "gut microbiota" refers to a set of many microorganisms [mainly bacteria], which live symbiotically within the human host. The term "microbiome" means the collective genomic content of these microorganisms. The number of bacterial cells within the gut microbiota exceeds the host's cells; collectively and their genes quantitatively surpass the host's genes. Immense scientific research into the nature and function of the gut microbiota is unraveling its roles in certain human health activities such as metabolic, physiology, and immune activities and also in pathologic states and diseases. Interestingly, the microbiota, a dynamic ecosystem, inhabits a particular environment such as the human mouth or gut. Human microbiota can evolve and even adapt to the host's unique features such as eating habits, genetic makeup, underlying diseases, and even personalized habits. In the past decade, biologists and bioinformaticians have concentrated their research effort on the potential roles of the gut microbiome in the development of human diseases, particularly immune-mediated diseases and colorectal cancer, and have initiated the assessment of the impact of the gut microbiome on the host genome. In the present chapter, we focus on the biological features of gut microbiota, its physiology as a biological factory, and its impacts on the host's health and disease status.

Green Biologics: Harnessing the Power of Plants to Produce Pharmaceuticals.

Plants are increasingly used for the production of high-quality biological molecules for use as pharmaceuticals and biomaterials in industry. Plants have proved that they can produce life-saving therapeutic proteins (Elelyso™-Gaucher's disease treatment, ZMapp™-anti-Ebola monoclonal antibodies, seasonal flu vaccine, Covifenz™-SARS-CoV-2 virus-like particle vaccine); however, some of these therapeutic proteins are difficult to bring to market, which leads to serious difficulties for the manufacturing companies. The closure of one of the leading companies in the sector (the Canadian biotech company Medicago Inc., producer of Covifenz) as a result of the withdrawal of investments from the parent company has led to the serious question: What is hindering the exploitation of plant-made biologics to improve health outcomes? Exploring the vast potential of plants as biological factories, this review provides an updated perspective on plant-derived biologics (PDB). A key focus is placed on the advancements in plant-based expression systems and highlighting cutting-edge technologies that streamline the production of complex protein-based biologics. The versatility of plant-derived biologics across diverse fields, such as human and animal health, industry, and agriculture, is emphasized. This review also meticulously examines regulatory considerations specific to plant-derived biologics, shedding light on the disparities faced compared to biologics produced in other systems.

A biotechnological approach for the production of new protein bioplastics.

The future of biomaterial production will leverage biotechnology based on the domestication of cells as biological factories. Plants, algae, and bacteria can produce low-environmental impact biopolymers. Here, two strategies were developed to produce a biopolymer derived from a bioengineered vacuolar storage protein of the common bean (phaseolin; PHSL). The cys-added PHSL* forms linear-structured biopolymers when expressed in the thylakoids of transplastomic tobacco leaves by exploiting the formation of inter-chain disulfide bridges. The same protein without signal peptide (ΔPHSL*) accumulates in Escherichia coli inclusion bodies as high-molar-mass species polymers that can subsequently be oxidized to form disulfide crosslinking bridges in order to increase the stiffness of the biomaterial, a valid alternative to the use of chemical crosslinkers. The E. coli cells produced 300 times more engineered PHSL, measured as percentage of total soluble proteins, than transplastomic tobacco plants. Moreover, the thiol groups of cysteine allow the site-specific PEGylation of ΔPHSL*, which is a desirable functionality in the design of a protein-based drug carrier. In conclusion, ΔPHSL* expressed in E. coli has the potential to become an innovative biopolymer.

Coding Therapeutic Nucleic Acids from Recombinant Proteins to Next-Generation Vaccines: Current Uses, Limitations, and Future Horizons.

This study aims to highlight the potential use of cTNAs in therapeutic applications. The COVID-19 pandemic has led to significant use of coding therapeutic nucleic acids (cTNAs) in terms of DNA and mRNA in the development of vaccines. The use of cTNAs resulted in a paradigm shift in the therapeutic field. However, the injection of DNA or mRNA into the human body transforms cells into biological factories to produce the necessary proteins. Despite the success of cTNAs in the production of corona vaccines, they have several limitations such as instability, inability to cross biomembranes, immunogenicity, and the possibility of integration into the human genome. The chemical modification and utilization of smart drug delivery cargoes resolve cTNAs therapeutic problems. The success of cTNAs in corona vaccine production provides perspective for the eradication of influenza viruses, Zika virus, HIV, respiratory syncytial virus, Ebola virus, malaria, and future pandemics by quick vaccine design. Moreover, the progress cTNAs technology is promising for the development of therapy for genetic disease, cancer therapy, and currently incurable diseases.

Microalgae, Seaweeds and Aquatic Bacteria, Archaea, and Yeasts: Sources of Carotenoids with Potential Antioxidant and Anti-Inflammatory Health-Promoting Actions in the Sustainability Era

Carotenoids are a large group of health-promoting compounds used in many industrial sectors, such as foods, feeds, pharmaceuticals, cosmetics, nutraceuticals, and colorants. Considering the global population growth and environmental challenges, it is essential to find new sustainable sources of carotenoids beyond those obtained from agriculture. This review focuses on the potential use of marine archaea, bacteria, algae, and yeast as biological factories of carotenoids. A wide variety of carotenoids, including novel ones, were identified in these organisms. The role of carotenoids in marine organisms and their potential health-promoting actions have also been discussed. Marine organisms have a great capacity to synthesize a wide variety of carotenoids, which can be obtained in a renewable manner without depleting natural resources. Thus, it is concluded that they represent a key sustainable source of carotenoids that could help Europe achieve its Green Deal and Recovery Plan. Additionally, the lack of standards, clinical studies, and toxicity analysis reduces the use of marine organisms as sources of traditional and novel carotenoids. Therefore, further research on the processing of marine organisms, the biosynthetic pathways, extraction procedures, and examination of their content is needed to increase carotenoid productivity, document their safety, and decrease costs for their industrial implementation.

Bacterial Biological Factories Intended for the Desulfurization of Petroleum Products in Refineries

The removal of sulfur by deep hydrodesulfurization is expensive and environmentally unfriendly. Additionally, sulfur is not separated completely from heterocyclic poly-aromatic compounds. In nature, several microorganisms (Rhodococcus erythropolis IGTS8, Gordonia sp., Bacillus sp., Mycobacterium sp., Paenibacillus sp. A11-2 etc.) have been reported to remove sulfur from petroleum fractions. All these microbes remove sulfur from recalcitrant organosulfur compounds via the 4S pathway, showing potential for some organosulfur compounds only. Activity up to 100 µM/g dry cell weights is needed to meet the current demand for desulfurization. The present review describes the desulfurization capability of various microorganisms acting on several kinds of sulfur sources. Genetic engineering approaches on Gordonia sp. and other species have revealed a variety of good substrate ranges of desulfurization, both for aliphatic and aromatic organosulfur compounds. Whole genome sequence analysis and 4S pathway inhibition by a pTeR group inhibitor have also been discussed. Now, emphasis is being placed on how to commercialize the microbes for industrial-level applications by incorporating biodesulfurization into hydrodesulfurization systems. Thus, this review summarizes the potentialities of microbes for desulfurization of petroleum. The information included in this review could be useful for researchers as well as the economical commercialization of bacteria in petroleum industries.

Photosynthetic Polymer Dots–Bacteria Biohybrid System Based on Transmembrane Electron Transport for Fixing CO2 into Poly-3-hydroxybutyrate

Organic semiconductor-microbial photosynthetic biohybrid systems show great potential in light-driven biosynthesis. In such a system, an organic semiconductor is used to harvest solar energy and generate electrons, which can be further transported to microorganisms with a wide range of metabolic pathways for final biosynthesis. However, the lack of direct electron transport proteins in existing microorganisms hinders the hybrid system of photosynthesis. In this work, we have designed a photosynthetic biohybrid system based on transmembrane electron transport that can effectively deliver the electrons from organic semiconductor across the cell wall to the microbe. Biocompatible organic semiconductor polymer dots (Pdots) are used as photosensitizers to construct a ternary synergistic biochemical factory in collaboration with Ralstonia eutropha H16 (RH16) and electron shuttle neutral red (NR). Photogenerated electrons from Pdots promote the proportion of nicotinamide adenine dinucleotide phosphate (NADPH) through NR, driving the Calvin cycle of RH16 to convert CO2 into poly-3-hydroxybutyrate (PHB), with a yield of 21.3 ± 3.78 mg/L, almost 3 times higher than that of original RH16. This work provides a concept of an integrated photoactive biological factory based on organic semiconductor polymer dots/bacteria for valuable chemical production only using solar energy as the energy input.

Lysinibacilli: A Biological Factories Intended for Bio-Insecticidal, Bio-Control, and Bioremediation Activities.

Microbes are ubiquitous in the biosphere, and their therapeutic and ecological potential is not much more explored and still needs to be explored more. The bacilli are a heterogeneous group of Gram-negative and Gram-positive bacteria. Lysinibacillus are dominantly found as motile, spore-forming, Gram-positive bacilli belonging to phylum Firmicutes and the family Bacillaceae. Lysinibacillus species initially came into light due to their insecticidal and larvicidal properties. Bacillus thuringiensis, a well-known insecticidal Lysinibacillus, can control many insect vectors, including a malarial vector and another, a Plasmodium vector that transmits infectious microbes in humans. Now its potential in the environment as a piece of green machinery for remediation of heavy metal is used. Moreover, some species of Lysinibacillus have antimicrobial potential due to the bacteriocin, peptide antibiotics, and other therapeutic molecules. Thus, this review will explore the biological disease control abilities, food preservative, therapeutic, plant growth-promoting, bioremediation, and entomopathogenic potentials of the genus Lysinibacillus.

Eukaryotic Microorganisms as Biological Factories for the Preparation of Metal Nanoparticles

The use of microorganisms as reducing and stabilizing agents in biogenic syntheses of metal nanoparticles is an attractive approach. There is a large number of potential bioagents able to yield big amounts of various biomolecules, and to prepare nanoparticles of diverse physicochemical properties. Microscopic fungi and algae are widely studied for the preparation of nanoparticles, mainly because of their ability to produce vast amounts of extracellular proteins, enzymes, and other metabolites that can actively participate in the metal reduction and also contribute to the nanoparticle stabilization. This results in highly stable metal nanoparticles with interesting properties that can be used, for example, as antimicrobial agents (especially Ag or Cu nanoparticles) or as catalysts. This review summarizes the main, promising representatives of microscopic fungi, yeasts, and algae used for the preparation of nanoparticles of various metals.

Characterisation of the Mentha canadensis R2R3-MYB transcription factor gene McMIXTA and its involvement in peltate glandular trichome development

BackgroundMentha canadensis L. has important economic value for the production of essential oils, which are synthesised, secreted and stored in peltate glandular trichomes. As a typical multicellular secretory trichome, glandular trichomes are important biological factories for the synthesis of some specialised metabolites. However, little is known about the molecular mechanism of glandular trichome development in M. canadensis.ResultsIn this study, the R2R3-MYB transcription factor gene McMIXTA was isolated to investigate its function in glandular trichome development. Bioinformatics analysis indicated that McMIXTA belonged to the subgroup 9 R2R3-MYB, with a R2R3 DNA-binding domain and conserved subgroup 9 motifs. A subcellular localisation assay indicated that McMIXTA was localised in the nucleus. Transactivation analysis indicated that McMIXTA was a positive regulator, with transactivation regions located between positions N253 and N307. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that McMIXTA formed a complex with McHD-Zip3, a trichome development-related HD-ZIP IV transcription factor. Overexpression of McMIXTA in Mentha × piperita L. caused an increase in peltate glandular trichomes density of approximately 25% on the leaf abaxial surface.ConclusionsOur results demonstrated that the subgroup 9 R2R3-MYB transcription factor McMIXTA has a positive effect on regulating peltate glandular trichome development and the MIXTA/HD-ZIP IV complexes might be conserved regulators for glandular trichome initiation. These results provide useful information for revealing the regulatory mechanism of multicellular glandular trichome development.

A New Strategy for Microbial Taxonomic Identification through Micro-Biosynthetic Gold Nanoparticles and Machine Learning.

Microorganisms can serve as biological factories for the synthesis of inorganic nanomaterials that can become useful as nanocatalysts, energy-harvesting-storage components, antibacterial agents, and biomedical materials. Herein, the development of biosynthesis of inorganic nanomaterials into a simple, stable, and accurate strategy for distinguishing microorganisms from multiple classification levels (i.e., kingdom, order, genus, and species) without gene amplification, biochemical testing, or target recognition is reported. Gold nanoparticles (AuNPs) biosynthesized by different microorganisms differ in color of the solution, and their features can be characterized, including the particle size, the surface plasmon resonance (SPR) spectrum, and the surface potential. The inter-relation between the features of micro-biosynthetic AuNPs and the classification of microorganisms are exploited at different levels through machine learning to establish a taxonomic model. This model agrees well with traditional classification methods that offers a new strategy for microbial taxonomic identification. The underlying mechanism of this strategy is related to the biomolecules produced by different microorganisms including glucose, glutathione, and nicotinamide adenine dinucleotide phosphate-dependent reductase that regulate the features of micro-biosynthetic AuNPs. This work broadens the application of biosynthesis of inorganic materials through micro-biosynthetic AuNPs and machine learning, which holds great promise as a tool for biomedical research.

Improvement of soybean cultivation technology in the southern forest-steppe of western Siberia

Legumes contribute significantly to the nitrogen balance of agrocenosis and terrestrial ecosystems. They fix the free air nitrogen and convert it into forms available to other plants. Legumes are a powerful biological factory of nitrogen fertilizers. The soils are enriched with available forms of nitrogen up to 80 kg/ha during the growing season. This process occurs due to the soil organic matter, stubble, and root residues left after harvesting soybeans. An increased planted area of soybeans in the rotation promotes a significant improvement in the growing conditions of other crops and increases their yield without additional costs. The crop yield is not significantly affected by soil treatment using herbicides in the conditions of the southern forest-steppe of Western Siberia. It is impossible to reduce the infestation of soybean crops to an economically harmless level with the use of a single herbicide. Due to a single application of herbicide and nitrogen-phosphate fertilizers, the yield of soybeans increases by an average of 0.46 t/ha or 51.7%.

Regulation of biological balance between pests and their entomophages in biological protection of cotton

The issues of regulation of biological balance between the main pests of cotton and their entomophages in biological protection are considered. The ways and methods of developing optimal work plans of biological factories for the production of useful entomofauna (trichogram, brackon, golden-eyed) against cotton pests (cotton and winter scoops) for various zones of the republic using mathematical modeling and programming methods are determined.

Cricket: The third domesticated insect.

Cricket: The third domesticated insect.

Carotenoid Production from Microalgae: Biosynthesis, Salinity Responses and Novel Biotechnologies.

Microalgae are excellent biological factories for high-value products and contain biofunctional carotenoids. Carotenoids are a group of natural pigments with high value in social production and human health. They have been widely used in food additives, pharmaceutics and cosmetics. Astaxanthin, β-carotene and lutein are currently the three carotenoids with the largest market share. Meanwhile, other less studied pigments, such as fucoxanthin and zeaxanthin, also exist in microalgae and have great biofunctional potentials. Since carotenoid accumulation is related to environments and cultivation of microalgae in seawater is a difficult biotechnological problem, the contributions of salt stress on carotenoid accumulation in microalgae need to be revealed for large-scale production. This review comprehensively summarizes the carotenoid biosynthesis and salinity responses of microalgae. Applications of salt stress to induce carotenoid accumulation, potentials of the Internet of Things in microalgae cultivation and future aspects for seawater cultivation are also discussed. As the global market share of carotenoids is still ascending, large-scale, economical and intelligent biotechnologies for carotenoid production play vital roles in the future microalgal economy.