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0INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
OVERVIEW OF MICROBIAL BIOSYNTHESIS FOCUSING ON
VITAL NATURAL PRODUCTS
1Shahzadi Bano, 2Jamal Akhtar Ansari, 3Farogh Ahsan, 4Abdul Rahman Khan
1Research Scholar, Department of Chemistry, Integral University, Dasauli, Kursi Road, Lucknow (India)-226026, 2Assistant Professor, Department of Chemistry, Integral University, Dasauli, Kursi Road, Lucknow (India)-226026, 3Department of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow (India)-226026, 4Professor & Head, Department of Chemistry, Integral University, Dasauli, Kursi Road, Lucknow (India)-226026 https://doi.org/10.5281/zenodo.13832456
Introduction
Microorganisms have existed on Earth for about 3.5 to 4 billion years, constantly evolving and adapting to new environments, and they can be found everywhere. Their presence has played a crucial role in the development of new ecosystems, some of which have paved the way for the evolution of more complex life forms [1]. Microorganisms can communicate with each other, and some produce signals that help form metabolically diverse communities. Without their metabolism and communication, the recycling of essential nutrients on Earth would cease. When faced with harsh conditions, microorganisms adapt and produce secondary metabolites that are vital to their life cycles. These secondary metabolites also have potential applications in medicine, industry, and disease treatment and prevention [2]. Biosynthesis is the process by which living microorganisms modify or combine simple molecules to create larger macromolecules [3]. Natural products, which are unique organic compounds produced by microorganisms as end products of secondary metabolism, have applications in alternative medicine, cosmetics, dietary supplements, and drug discovery [4]. This article explores various biosynthetic processes and secondary metabolites produced by microorganisms, as well as the potential importance of natural products in pharmaceutical, medicinal, and industrial biotechnology.
Brief history
Microorganisms are tiny communities that can only be seen with a microscope. These organisms, whether they are natural isolates, lab-selected mutants, or genetically engineered strains, are used in the production of vitamins, amino acids, enzymes, and various fermented products like sour cream, yogurt, buttermilk, pickles, sauerkraut, bread, and alcoholic beverages. They are also essential in the production of pharmaceuticals that cannot be manufactured through other means, including human hormones like insulin, antiviral substances such as interferon, various blood-clotting factors, clot-dissolving enzymes, and several vaccines [5].
The term "microbiology" was originally linked to the study of the causes of infectious diseases. However, as the field developed, it led to significant practical applications of microorganisms across various scientific disciplines. In the mid-1600s, shortly after the invention of the microscope, English scientist Robert Hooke made important observations about microorganisms [6].
Biocatalysis, a key component of biotechnology, broadly refers to the use of enzymes (biocatalysts) to facilitate or accelerate specific chemical reactions. Microbial catalysts have long been employed in the food industry and are now expanding into various fields, including industrial chemistry [7]. Biocatalysis utilizes whole microbial cells, cell extracts, purified enzymes,
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
immobilized cells, or immobilized enzymes. Recent advancements in large-scale genome sequencing, directed evolution, protein expression, metabolic engineering, high-throughput screening, and structural biology have driven rapid progress in biocatalysis [8]. The global market for industrial enzymes reached $3.3 billion in 2010 and grew to approximately $4.4 billion by 2015 [9]. Among these, technical enzymes are commonly used in bulk applications within the detergent, textile, pulp and paper, and biofuels industries. The leather and bioethanol sectors, in particular, generate the highest sales. Revenues from technical enzymes were nearly $1.2 billion in 2011, $1.5 billion in 2015, and are projected to reach $1.27 billion in 2021 [9], with the biofuels (bioethanol) market expected to lead in sales.
Biosynthesis
Biosynthesis process requires a series of chemical reactions, with precursor compounds, catalytic enzymes, cofactors, and chemical energy playing essential roles [10]. Bioactive microbial metabolites are notable for their interaction with the environment and their unique chemical structures [9]. Natural products, including microbial metabolites, can be used in three primary ways: (1) applied directly in medicine, agriculture, or other fields; (2) used as starting materials for chemical or microbiological modifications (derivatization); and (3) as lead compounds for chemical synthesis of new analogs or templates in rational drug design studies [2]. Research into the biosynthetic pathways of bacteria and fungi has shown that many protein factors are involved in biosynthesis. The regulation of these pathways, which includes macromolecular interactions and the control of specific enzymes and catalytic reactions, is well-documented in bacteria and fungi. Biological systems generate chemical diversity, with some biosynthetic pathways producing a single metabolite, while others are more flexible, generating a variety of compounds [11].
Primary biosynthetic product
Primary metabolites are produced during the exponential growth phase as typical end products of primary metabolism. In this process, the production curve aligns with the growth curve, with metabolites like vitamins, amino acids, and nucleosides being generated to support cell growth [12]. Examples of primary metabolites are provided below.
Vitamin
Microorganisms synthesize vitamins and other growth-stimulating compounds using the chemical constituents of the culture medium. These compounds are produced in excess of the microorganisms' needs, accumulate in the cultures, and are subsequently recovered. Microorganisms are commercially utilized to produce vitamins on a large scale under various cultural conditions [13]. Examples of vitamins produced through microbial processes include carotene, a precursor of Vitamin A from Blakeslea trispora; riboflavin from Ashbya gossypii; L-sorbose, used in Vitamin C synthesis, from Gluconobacter oxidans; and Vitamin B12 from Bacillus coagulans, Bacillus megaterium, Pseudomonas denitrificans, and Streptomyces olivaceus
[14].
Amino acid
Microbial fermentation of substrates such as glucose, acetate, and sucrose by different microorganisms can produce amino acids like D- and L-alanine, L-glutamic acid, L-leucine, L-lysine, and L-threonine. For example, Microbacterium ammoniaphilum ferments glucose to
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
produce D- and L-alanine, Micrococcus glutamicus generates L-glutamic acid from glucose, and Brevibacterium lactofermentum yields L-leucine. Brevibacterium flavum ferments acetate to produce L-lysine, while Escherichia coli K12 converts glucose into L-threonine. Additionally, primary metabolites like L-glutamate and L-lysine, which are often used as dietary supplements, are obtained through the mass production of Corynebacterium glutamicum [9].
Organic acids
Penicillium and Aspergillus have been employed in organic acid production. Organic acids are utilized across various industries and research fields. For instance, acetic acid is used in the food industry and for research purposes, fumaric acid is employed in resin production, and the calcium, iron, and potassium salts of gluconic acid are used in medicines and cleaning products. Lactic acid finds applications in the food industry (e.g., for fruit extracts, syrups, and pickles), as a dye mordant, in tanning, in skin decalcification, and in plastics, as well as in medicine in the form of calcium and iron lactates. Citric acid is used in the food industry (e.g., for fruit drinks, confectioneries, jams, jellies, preserved fruits, and candies), in pharmacy (e.g., for blood transfusions and effervescent products), in cosmetics (e.g., in astringent lotions, shampoos, and hair setting fluids), and in various industries (e.g., electroplating, leather tanning, pipe cleaning, and reactivation of old oil wells) [15].
Secondary biosynthetic product
Biological structures have long inspired solutions to technical challenges in fields like architecture, mechanical engineering, and materials science. Nature has created materials and biopolymers with exceptional properties. A natural product is something that occurs naturally and is not artificially made, often implying purity. Metabolic pathways in living systems fall into two main categories: those that produce a few specific chemicals, and those that generate a wide range of metabolites. The latter, known as diversity-generating pathways, are responsible for many small molecules in living systems. These pathways do not produce a single end product; instead, they involve enzymes with broad substrate specificities that handle various compounds [16].
Biopolymer
Biopolymers are large molecules made from monomeric units, bonded covalently, and produced by living organisms, making them biodegradable. These polymers can be derived from various biological sources like microorganisms, plants, or trees. Their structure, biocompatibility, and biodegradability are crucial to their function. Microorganisms produce various biopolymers, such as polysaccharides, polyesters, and polyamides, with physical properties dependent on their composition and molecular weight. Bacteria, for example, produce different polysaccharides, which can be classified by their biological functions: intracellular storage (e.g., glycogen), capsular (linked to the cell surface), and extracellular polysaccharides (e.g., xanthan, alginate, cellulose). These biopolymers, synthesized through various biosynthetic pathways, are encoded by specific gene clusters in the producing organisms. Due to their superior material properties, biocompatibility, and biodegradability, biopolymers have numerous medical and industrial applications, where they can enhance the performance of other biologically active molecules or be modified for various uses [17].
Antimicrobial Natural product
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
Microorganisms like bacteria, fungi, and mold produce various antimicrobial secondary metabolites that can inhibit other microorganisms. These metabolites are typically synthesized after the active growth phase to outcompete other organisms in the same ecological niche. For example, secondary metabolites from bacteria and fungi, such as penicillins and tetracyclines, are widely used as antibiotics. Antimicrobial agents encompass all substances that act against bacteria, viruses, and fungi. Filamentous microorganisms like fungi and actinomycetes are the primary sources of antibiotic secondary metabolites [18].
Bacterial Survival Strategies
Microorganisms can be either beneficial or harmful, and understanding the stress factors they encounter and their resistance mechanisms is crucial for biotechnology. Under stress, bacteria produce specific proteins that help them survive and adapt to harsh conditions, acting as molecular markers of stress. These stress-adapted bacteria can cause food spoilage and pose significant risks to public health, especially in developing countries. Foodborne pathogens can survive and thrive in various environments, forming biofilms on surfaces in food processing plants and medical devices. Their survival and growth depend on factors like pH, temperature, and the presence of antimicrobials. Some bacteria can produce spores, making them more resistant to adverse conditions [19].
Conclusion
Concerns about safe, healthy food have driven research into replacing chemical compounds with green biomaterials. Studies are exploring methods for producing renewable monomers and polymers, focusing on their benefits and drawbacks. There is a growing need for green substitutes in food, medicine, and pharmaceuticals. Microbial synthesis, particularly biosynthesis, is gaining attention due to its efficiency and ability to produce essential primary and secondary metabolites. Green chemistry approaches using microorganisms offer advantages like ease of scaling up, economic viability, and health safety.
REFERENCE
[1]Okasha N. Enhancement of magnetization of Mg-Mn nanoferrite by y-irradiation. J Alloys Compd Elsevier 2010; 490(1-2):307-10.
[2]Gupta C, Prakash D, Gupta S. Natural useful therapeutic products from microbes. J Microbiol Exp MedCrave Publishing 2014; Volume 1(Issue 1):23-37.
[3]Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell,. Molecular Biology of the Cell 2007[0nline] WW. Norton & Company: New york 2007.
[4]Singla RK, Dubey HD, Dubey AK. Therapeutic Spectrum of Bacterial Metabolites. Indo Glob J Pharm Sci 2014; 4(2):52-64.
[5]Wienhues A. Looking through the microscope: Microbes as a challenge for theorising biocentrism within environmental ethics. Endeavour Elsevier Current Trends 2022; 46(1-2):100819.
[6]Wang J, Vermerris W. Antimicrobial Nanomaterials Derived from Natural Products—A Review. Materials (Basel) Multidisciplinary Digital Publishing Institute (MDPI) 2016; 9(4):255-68.
[7]Wohlgemuth R. Biocatalysis--key to sustainable industrial chemistry. Curr Opin
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
Biotechnol Curr Opin Biotechnol 2010; 21(6):713-24.
[8]Sanchez-Garcia L, Martin L, Mangues R, et al. Recombinant pharmaceuticals from microbial cells: a 2015 update. Microb Cell Fact BMC 2016; 15(1):33-42.
[9]Adrio JL, Demain AL. Microbial Enzymes: Tools for Biotechnological Processes. Biomolecules Multidisciplinary Digital Publishing Institute (MDPI) 2014; 4(1):117-28.
[10] Vital and health statistics. "Control Mechanisms of protein-protein interactions in biosynthetic pathways of bacteria and fungi." Appl Sci Reports Progressive Science Publications 2016; 14(3):112-24.
[11] Fröhlich EE, Fröhlich E. Cytotoxicity of Nanoparticles Contained in Food on Intestinal Cells and the Gut Microbiota. Int J Mol Sci Multidisciplinary Digital Publishing Institute (MDPI) 2016; 17(4):509-19.
[12] Tianero MD, Pierce E, Raghuraman S, et al. Metabolic model for diversity-generating biosynthesis. Proc Natl Acad Sci US A National Academy of Sciences 2016; 113(7):1772-77.
[13] Tajkarimi M, Ibrahim SA. Antimicrobial activity of ascorbic acid alone or in combination with lactic acid on Escherichia coli O157:H7 in laboratory medium and carrot juice. Food Control Elsevier 2011; 22(6):801-04.
[14] Garg N, Aeron A. Microbes in process,. 2014[Online] Nova Science Publishers, Inc. 2014.
[15] Baweja M, Nain L, Kawarabayasi Y, et al. Current technological improvements in enzymes toward their biotechnological applications. Front Microbiol Frontiers Research Foundation 2016; 7(JUN):206451.
[16] Li B, Sher D, Kelly L, et al. Catalytic promiscuity in the biosynthesis of cyclic peptide secondary metabolites in planktonic marine cyanobacteria. Proc Natl Acad Sci U S A Proc Natl Acad Sci U S A 2010; 107(23):10430-35.
[17] Adsul M, Tuli DK, Annamalai PK, et al. Polymers from Biomass: Characterization, Modification, Degradation, and Applications. Int J Polym Sci Hindawi Limited 2016; 2016:1857297.
[18] Raman M, Ambalam P, Kondepudi KK, et al. Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer. Gut Microbes Gut Microbes 2013; 4(3):181-92.
[19] Boor KJ. Bacterial Stress Responses: What Doesn't Kill Them Can Make Them Stronger. PLoS Biol PLOS 2006; 4(1):0018-20.
