how secondary metabolites are produced

Full Answer

What are the types of secondary metabolites production in bioreactors?

This article throws light upon the seven types of secondary metabolites production in bioreactors. The seven production types are: (1) Shikonin Production (2) Berberine Production (3) Rosmarinic Acid Production (4) Indole Alkaloids Production (5) Organ Culture (6) Hairy Root Culture and (7) Commercialization. Production Type # 1.

When are secondary metabolites produced in microorganisms?

They are produced during the late growth phase of the microorganisms. The secondary metabolite production is controlled by special regulatory mechanisms in microorganisms, as their production is generally repressed in logarithmic phase and depressed in stationary growth phases.

What are the sources of novel secondary metabolites?

For eg., antibiotics, toxins, pheromones, enzyme inhibitors, etc. Streptomycetes and related actinomycetes are the sources of novel secondary metabolites. Required for growth and maintenance of cellular function. Involved in ecological functions. Occurs at the growth phase. Occurs at the stationary phase.

How do secondary plant metabolites exert their action?

Eventually, secondary plant metabolites exert their action on molecular targets that differ from one case to the other. These targets may be enzymes, mediators, transcription factors or even nucleic acids.

When are secondary metabolites synthesized?

Secondary metabolites are synthesized during the end or near the stationary phase of growth and are not involved in cell growth, development, or reproduction (Crueger and Crueger, 1990; Jit and Garg, 2015 ).

Which organisms produce the most secondary metabolites?

Comparatively, a few microbial organisms produce the majority of secondary metabolites and a single microbial type has the capacity to produce very different metabolites, for example, Streptomyces griseus and Bacillus subtilis each can produce more than 50 different secondary metabolites.

What are the effects of SMs on plants?

Plant SMs are important compounds that add color, taste, and odor to plants and also mediate plant responses to adverse environmental conditions ( Verma and Shukla, 2015 ). A number of factors cause significant perturbations in the production of SM in plants. The endogenous levels of different SMs vary among different plant species and also within the same plant species ( Barton, 2007 ). A number of cellular and biochemical factors influence the storage and transportation of SM. Developmental factors influence the initiation and subsequent differentiation of particular cellular structures involved in the biosynthesis and storage of SM ( Broun et al., 2006 ). Furthermore, the endogenous levels of SM are also influenced by a number of environmental stresses such as nutrient deficiencies, wounding, metal ions, ultraviolet (UV) radiation, light, circadian rhythm, seasonality, salinity, drought, and temperature ( Gouvea et al., 2012; Verma and Shukla, 2015 ). Apart from this, the endogenous concentration of SM is associated with the metabolic pathway of the particular SM and growth conditions ( Akula and Ravishankar, 2011 ). The concentration of SM is also affected by biotic factors (pathogen attack) and thereby mediates plant defense mechanism. For instance, there exists a significant variation in the levels of phenolics in plants in response to environmental stresses such as light intensity and nutrient availability ( Verma and Shukla, 2015 ).

What is the process of producing metabolites?

The network of metabolites, working with enzyme reactions during the entire process of metabolism, is called the metabolome [10]. The metabolome involves/implicates all the series of combinations of cascading reactions between enzymes and substrates in the steps of metabolism, and ending in the production of the primary and secondary metabolites.

What is the idiophase of fermentation?

Secondary metabolites usually accumulate during the later stage of fermentation, known as the idiophase, which follows the active growth phase called the trophophase. Compounds produced in the idiophase have no direct relationship to the synthesis of cell material and normal growth of the microorganisms.

Why are secondary metabolites important?

These plant secondary metabolites are important candidates for human nutrition. A number of plant secondary metabolites possess antioxidant properties that act as the first line of defense against oxidative damage induced by different environmental (including high temperature) constraints.

What are the most important secondary metabolites?

The most important secondary metabolites have been the anti-infective drugs and, among these, the β-lactams are the most important class. Other important classes include the aminoglycosides, tetracyclines, macrolides, lipopeptides, polyenes, and the echinocandins. Successful microbial secondary metabolites include many used to combat cancer, ...

What are secondary metabolites?

Secondary metabolites are not essential for growth and development of plant but these are required for the survival of plants in unfavorable environment. Secondary metabolites are important for flower color or volatile, flavor of food, attraction of pollinator, interaction with symbiotic microorganisms, and tolerance against pest and diseases (isofalvonoids and phenylpropanoid derivatives). These are also take part in the mechanism of frost tolerance, nutrient storage, structural reinforcement, photo protective, UV–Vis absorption, signaling to mutualist, and in the adaptation of the plant under various environmental conditions and stress (Singer et al., 2003; Verpoorte et al., 2002 ). Presently, secondary metabolites (morphine, digitoxin, salicylic acid, etc.) are also important for their health improving effects and disease preventing activities such as antioxidant and cholesterol lowering (lovastatin) properties. Secondary metabolites such as terpene, used as antibacterial, insecticide (pyrethrin), antifungal, antitumoric (bleomycin), antimicrobial (pentacyclic terpene arjunolic acid), antibiotic (penicillin, vancomycin) and anticancer (taxol) compounds. Because of these properties, these molecules are used as fine chemicals such as drug, flavors, dye, fragrance, and insecticides ( Table 9.1) ( Verpoorte et al., 2002; Sangwan et al., 2001; Sangwan and Sangwan, 2014; Sangwan et al., 2007a,b ). Some plants, such as Withania, Centella, Artemisia, Cymbopogon, etc. possess medicinally important phytoconstituents like withanolides, withaferin, withanone, asiaticoside, madecassoside, artemisinin, essential oil, etc. These compounds have tremendous significance as drugs ( Chaurasiya et al., 2012; Sangwan et al., 1993, 2004, 2007a,b, 2008, 2010, 2013b; Sangwan and Sangwan, 2007, 2014 ). Moreover in the year 2015, in Physiology and Medicine Noble prize has been awarded to Youyou Tu for discovering the artemisinin, a potential antimalarial drug, isolated from Artemisia annua ( Su and Miller, 2015 ).

What is a microbial secondary metabolite?

Notwithstanding this debate, microbial secondary metabolites are often described as low molecular weight, bioactive compounds, which are usually produced and ex creted by microbes during a particular period or phase of their growth cycle [25,27].

What are the secondary metabolites of antibiotics?

Microbial seconda ry metabolites are the well-known examples of FDA approved antibiotics. The sources of majority of these antibiotics are actinobacteria—a class of Gram-positive bacteria. Bioactive secondary metabolite secretions of these actinobacteria display a promising potential to be used as anticancerous, antituberculosis, and antimicrobial drugs. Due to the high rediscovery rate of known compounds from actinobacteria inhabiting conventional environments, there has been a renewed interest in the exploration of untapped regions of the Himalayas, more specifically the Northwestern Himalayas, for the development of new secondary metabolites for rare and novel actinobacteria with regard to the urgent need to combat the increasing number of multidrug-resistant human pathogens. By exploiting actinobacteria from these high-altitude Himalayan regions, attempts to isolate either novel taxa of actinobacteria or known actinobacteria with novel bioactive secondary metabolites are gaining success. These metabolites are potential sources for the discovery of biologically active compounds.

Why is the production of SMs limited?

Production of SMs is frequently limited due to a negative effect exerted by the carbon source on the synthesis of many SMs. This regulatory mechanism is termed carbon catabolite regulation (CCR). There are many examples of enzymes and secondary metabolites regulated by CCR in bacteria and fungi.

How does SMs start?

From studies in liquid medium, it is now known that production of SMs starts when growth is limited by the exhaustion of one key nutrient: carbon, nitrogen, or phosphate source (nutritional shift-down). For example, penicillin biosynthesis by Penicillium chrysogenum starts when glucose is exhausted from the culture medium and the fungus starts consuming lactose, a less readily utilized sugar [3]. Thus, the culture is directed toward a relatively short growth phase, and a long and efficient production phase. In other words, different products (unary metabolites, enzymes, etc.) need different fermentation process design and control.

Why is it important to consider that the product is a SM and also its regulation?

Consequently, it is important to consider that the product is a SM and also its regulation, to design an efficient process, with the appropriate limiting nutrient (s). Moreover, the understanding of the regulation of SMs has traditionally been the basis for the process design and also an aid in developing production strains.

Can microorganisms survive without metabolites?

In other words, the producer organisms (or microorganisms) can survive and proliferate without synthesizing these metabolites; on the contrary, primary metabolites, almost universally distributed, are vital for the normal functioning of cells. This definition by exclusion, first proposed by Kossel [26] more than a century ago, has been the subject of a strong controversy.

Which organisms produce the most secondary metabolites?

Comparatively, a few microbial organisms produce the majority of secondary metabolites and a single microbial type has the capacity to produce very different metabolites, for example, Streptomyces griseus and Bacillus subtilis each can produce more than 50 different secondary metabolites.

What are the most common secondary metabolites?

The most common secondary metabolites are antibiotics; others include mycotoxins, ergot alkaloids, the widely used immunosuppressant cyclosporin, and fumagillin, an inhibitor of angiogenesis ...

What are the two metabolites that are used to treat cancer?

Successful microbial secondary metabolites include many used to combat cancer, such as the anthracycline doxorubicin and bleomycin. Antitumor agents from plants that have been very useful are taxol and camptothecin.

What transcription factors are involved in SM clusters?

Many SM clusters contain a gene encoding a transcription factor specific for activating the enzymatic genes in the cluster. The hallmark transcription factor is AflR, encoded by a gene in the aflatoxin and sterigmatocystin (ST) clusters in various Aspergillus spp. Overexpression of aflR leads to enhanced expression of SM cluster genes and concomitant metabolite production (Flaherty & Payne, 1997). This method can be used to enhance production of SMs (reviewed in Yin & Keller, 2011 ). More recently, it has been shown that some SM cluster transcription factors can activate more than one SM cluster. In A. nidulans, induced expression of ScpR induced expression not only of inp cluster genes but also of the afo cluster genes (Bergmann et al., 2010), and A. nidulans aflR is involved in both ST and asperthecin biosynthesis (Yin et al., 2012).

What are secondary metabolites of fungi?

Fungal QSIs are considerably important for drug and food industry. Patulin and penicillic acid are reported secondary metabolites with QSI potentials from Penicillium radicicola and Penicillium coprobium by Rasmussen et al. (2005). These mycotoxins were found to modulate QS related genes in P. aeruginosa, indicating their QSI activities (45% and 60% inhibition by patulin and penicillic acid, respectively). Also, they detected that patulin could increase the potential of tobramycin against biofilm forms. This compound was also found to be considerably effective in the clearance of P. aeruginosa in a mouse model of pulmonary infection when compared with a control group.

Why is it important to consider that the product is a SM and also its regulation?

Consequently, it is important to consider that the product is a SM and also its regulation, to design an efficient process, with the appropriate limiting nutrient (s). Moreover, the understanding of the regulation of SMs has traditionally been the basis for the process design and also an aid in developing production strains.

What is the difference between primary and secondary metabolites?

The difference between primary and secondary metabolite is ambiguous since many of the intermediates in primary metabolism is overlapping with the intermediates of secondary metabolites [ 2 ]. Amino acids though considered a product of primary metabolite are definitely secondary metabolite too. Contrary to the observation that sterols are secondary metabolites that are indispensable part of many structural framework of a cell. The mosaic nature of an intermediate indicates common biochemical pathway being shared by primary and secondary metabolism [ 3 ]. The secondary metabolites serve as a buffering zone into which excess C and N can be shunted into to form inactive part of primary metabolism. The stored C and N can revert back to primary metabolite by the metabolic disintegration of secondary metabolite when on demand. There is dynamism and a delicate balance between the activities of the primary and secondary metabolism ( Figure 1) being influenced by growth, tissue differentiation and development of the cell or body, and also external pressures [ 4 ].

How many secondary metabolites are there?

Over 2,140,000 secondary metabolites are known and are commonly classified according to their vast diversity in structure, function, and biosynthesis. There are five main classes of secondary metabolites such as terpenoids and steroids, fatty acid-derived substances and polyketides, alkaloids, nonribosomal polypeptides, and enzyme cofactors [ 6 ].

What are secondary metabolites used for?

Predominantly, the secondary metabolites are used for variety of biological activities like antimicrobial and antiparasitic agents, enzyme inhibitors and antitumor agent, immunosuppressive agents, etc. [ 7 ].

Why are secondary metabolites important?

The battle against any disease is a vibrant symmetry between advances in chemotherapy and natural selection on infectious or invasive agents. If the scientific community is to put constant importance in this never ending effort, then new sources of bioactive secondary metabolites with novel activities must be found. Secondary metabolites are one of their essential means of growth and defense , and these metabolites are readily available for discovery. Secondary metabolites with noteworthy biological activity are considered as an alternative to most of the synthetic drugs and other commercially valuable compounds.

What is the sum of all the biochemical reactions carried out by an organism?

Introduction. The metabolism can be defined as the sum of all the biochemical reactions carried out by an organism. Metabolites are the intermediates and products of metabolism and are usually restricted to small molecules.

How many compounds are there in alkaloids?

There are over 12,000 known compounds of alkaloids, and their basic structures consist of basic amine group and are derived biosynthetically from amino acids.

Which metabolic pathway branch out from primary metabolism?

Secondary metabolites branch out from the pathways of primary metabolism. Commercially, important secondary and primary metabolic pathways are given in Table 4.

How many types of secondary metabolites are there in bioreactors?

This article throws light upon the seven types of secondary metabolites production in bioreactors.

Which alkaloids are released into the medium in T. minus?

In contrast with cell cultures of T. minus, Coptis japonica and Berberis aristata cells in culture accumulated most of the protoberberine alkaloid in the cells and released only a small amount of alkaloids into the medium, when partial autolysis of senescent cells occurred.

Where is berberine produced?

Shikonin, a natural dye, is produced by Mitsui Petrochemcal Industries. Berberine is sold exclusively in Asia and can be produced commercially in a continuous-flow bioreactor in which cells are retained by a membrane and harvested periodically.

Is technology needed for secondary metabolites?

Technology for the production of useful secondary metabolites has come to a threshold level. A final push is required to make this technology widely applicable for the production of pharmaceuticals, dyes and fragrances, demand for natural products for fragrances, dyes and pharmaceuticals (anti-AIDS, anti-aging, anti cancer etc.), technology should be ready to meet the demand in coming decades.

Where are secondary metabolites formed?

Secondary metabolites are formed near the stationary phase of growth and are not involved in growth, reproduction and development.

What are the sources of novel secondary metabolites?

For eg., antibiotics, toxins, pheromones, enzyme inhibitors, etc. Streptomycetes and related actinomycetes are the sources of novel secondary metabolites .

What are Metabolites?

Metabolites are the intermediate products produced during metabolism, catalyzed by various enzymes that occur naturally within cells. Eg., antibiotics, and pigments. The term metabolites are usually used for small molecules. The various functions of metabolites include; fuel, structure, signalling, catalytic activity, defence and interactions with other organisms.

Why are secondary metabolites considered end products of primary metabolites?

Secondary metabolites are considered to be the end products of primary metabolites because they are derived by the pathways in which the primary metabolites involve. For eg., antibiotics, toxins, pheromones, enzyme inhibitors, etc. Streptomycetes and related actinomycetes are the sources ...

How many metabolites are there in the human body?

Human Metabolites. Humans have 2500 metabolites. Prostaglandin produces a metabolite Arachidonic acid. Both the molecules have the same physical properties, functional groups and are linked by a series of enzyme-catalyzed reactions. Cholesterol produces steroid hormones, catecholamines arise from the amino acid tyrosine.

What are the two types of metabolites?

Plant metabolites are of two types: 1 Primary Metabolites 2 Secondary Metabolites

What are the intermediate products of anabolic metabolism?

They are the intermediate products of anabolic metabolism, which are used by the cells for the formation of essential macromolecules. Amino acids, vitamins, organic acids, are some of the primary metabolites produced industrially. Alcohol is the major primary metabolite produced on a large scale, industrially.

Overview

Plant secondary metabolites

Plant secondary metabolites in medicine

Fungal secondary metabolites

Bacterial secondary metabolites

Biotechnological approaches

See also

External links