Fungal Metabolites

The biocontrol of plant pathogenic fungi includes two complementary approaches depending on whether the aim is to control soil-borne or air-borne pathogenic fungi. In the first case, natural biotic interactions within the indigenous microflora should be stimulated to regulate inoculum density and the infectious activity of pathogen populations. This strategy can be enhanced by inoculating one or more previously selected biocontrol agents. In the second case, one or more previously selected biocontrol agents can be sprayed on plant foliage to interfere with the development of the targeted pathogen through different mechanisms involving particular enzymes or metabolites. Selecting the most effective biological control agents implies (i) knowing the mechanisms of their interactions with the pathogens and (ii) checking that the environment in which the biocontrol agent is introduced will permit the expression of these mechanisms. The common thread of this chapter is the impressive diversity of metabolites and proteins produced by fungi and involved in interactions between pathogenic and nonpathogenic fungi. Many metabolites and proteins were discovered empirically or by chance a few decades ago, and what we knew about them was they inhibited the growth of pathogenic models on agar medium. Fungi producing these metabolites were not well-known fungal species and were not used as biocontrol agents. However, the demonstration of their intense metabolic activity paved the way for more investigations in this area and led to deciphering the mechanisms of interactions between fungal strains. Thus, in recent years a large number of enzymes, signal molecules, secondary metabolites, large-size proteins, as well as new metabolic pathways have been revealed by genomics, and it is now possible to understand why some strains can control a given pathogen more than others or stimulate plant defense reactions. To date, the most studied fungi include many strains of the genus Trichoderma but also the species Chlonostachys rosea, Coniothyrium minitans, Verticillium biguttatum, and the oomycete Pythium oligandrum. All of them are successfully used as biocontrol agents. This chapter does not aim to provide a comprehensive catalog, but rather to associate these metabolites and proteins to the modes of action involved in pathogen control. The state of the art presented in this review suggests promising prospects for rational, appropriate, and effective use of the biocontrol potential offered by the huge diversity of fungal metabolites and proteins.

Our environment is pervaded by a plethora of small exotic molecules, which are released without intermission by almost all organisms, like plants, microbes, or even animals. Plants and fungi are especially rich sources of these low-molecular-weight compounds, which are called secondary metabolites, and whose physiological functions are still mysterious in many cases. The number of the described compounds exceeds 100,000, and these molecules do not possess apparent importance in the producer’s life but regulate, modulate, induce, hinder, or even kill organisms other than the producer. Of course, these often unexpected substantial biological effects make these molecules so interesting and valuable. In this chapter, secondary metabolites from a plant and fungal interactions are surveyed considering hormones, antifungal metabolites, as well as the metabolites of mutualistic interactions observed between plants. Special secondary metabolites from biotrophic, necrotrophic, and specific interactions are also presented here, and their physiological and ecological roles and significances are discussed.

Fungal endophytes are known to produce secondary metabolites. The synthesis of vanillin and its precursors have never been clearly elucidated. Given fungi can produce such metabolites, it is speculated that fungal endophytes in vanilla could be contributing to vanillin and its precursors. An investigation was thus carried to find whether fungal endophytes are present in Vanilla planifolia. Additionally, vanilla flavor varies across cultivation regions; hence, the distribution of endophytes across regions was also assessed and found to differ. The metabolic changes brought by the fungi on vanillin and its precursors in vanilla pods were also evaluated. Out of 434 isolated fungal endophytes, two candidates emerged: Pestalotiopsis microspora and Diaporthe phaseolorum. However, P. microspora increased the most the absolute amounts (quantified by ¹H NMR in μmol/g DW green pods) of vanillin (37.0 × 10⁻³), vanillyl alcohol (100.0 × 10⁻³), vanillic acid (9.2 × 10⁻³), and p-hydroxybenzoic acid (87.9 × 10⁻³) when cultured on green pod-based media. Given the physical proximity of fungi inside pods, endophytic biotransformation may contribute to the complexity of vanilla flavors.

Aflatoxin B1 is one of the most hepatocarcinogenic naturally occurring compounds known, produced by toxic species of fungi in different types of food including rice. The contamination of food with this toxin could lead to a series of health problems and huge economic losses. Rice is the second largest quantity staple food and internationally traded cereal. Aflatoxin is produced in areas where climatic conditions are favorable to fungal growth and the production of aflatoxin affects plant growth and rice yield. The aim of this review article is to show and explain the levels of aflatoxin contamination of rice worldwide during the period 2004–2014. In general, aflatoxin levels in rice are low and vary from country to country. However, the high daily intake of rice makes even these lower levels of concern, as aflatoxin B₁ (AFB1) is carcinogenic and has been correlated with hepatocellular carcinoma (HCC) incidence in some countries. In addition to the increased distribution of aflatoxins in rice being addressed, the analytical procedures and the local and global permissible limits for aflatoxins are presented and discussed.

Mycotoxins are secondary metabolites produced by filamentous fungi which contaminate a large fraction of the world’s food, mainly staple foods such as corn, cereals, groundnuts, and tree nuts, besides meat, milk, and eggs. This worldwide contamination of foods is an enormous problem to human populations, principally in less industrialized countries and in the rural areas of some developed countries. The adverse effects of mycotoxins on human health can be both acute and chronic, provoking problems such as liver cancer, reduction of immunity, alterations in the protein metabolism, gangrene, convulsions, and respiratory problems, among others. The economic impact of mycotoxins in foods includes increased health care costs and premature deaths. Some factors which influence the presence of mycotoxins in foods are related to environmental conditions, such as storage, that can be controlled without too much expense. The cleaning of contaminated foods, on the hand, is economically costly and rarely implemented, so it tends to be carried out mainly in developing countries. Aflatoxins, ergot alkaloids, ochratoxins, 3-nitropropionic acid, fumonisins, trichothecenes, and zearelenone, are the most important economically, although dozens of other mycotoxins can also be associated with human health risks. Despite international attempts to improve and implement legislation to control the presence of mycotoxins in foods, its implementation has been ineffective.

Fungi possess all kinds of melanins found in nature. These pigments are products of polymerization of phenolic compounds. Phenolic precursors determine the polymerization products. Though formed via different precursors, polymerized melanins possess common properties. Melanin multifunctionality is well documented in fungi. Such functions of melanins as creating a tolerance to harsh environments are fulfilled in both saprophytes and parasites. But pathogenic fungi face double impact – hostile environment plus defenses of their hosts. Fungal melanin affords remarkable protection from many such factors and thus favors pathogenicity. Besides, pathogen melanins may act as an arm of aggression through involvement in parasite’s penetration and suppression of host’s responses. In outline, natural polymers of this group have irregular structure and perform effectively many biologically important functions related to high adaptive flexibility of their carriers.

Several filamentous fungi grow on the surface or inside different types of cheese, produce secondary metabolites, and contribute to the organoleptic characteristics of mature cheese. Particularly relevant is the contribution of Penicillium roqueforti to the maturation of blue-veined cheeses (Roquefort, Danablu, Cabrales, etc.). P. roqueforti is inoculated into these cheeses as a secondary starter. This fungus is closely related taxonomically to Penicillium carneum and Penicillium paneum, but these two species are not used as starters because they produce the potent toxin patulin. P. roqueforti Thom has the capability to produce about 20 secondary metabolites of at least seven different families, but it seems that only some of them are produced in microaerobic conditions and accumulate inside the cheese (e.g., andrastins). This article focuses on the biosynthetic pathways, gene clusters, and relevance of the known metabolites of P. roqueforti including roquefortines, PR-toxin and eremofortins, andrastins, mycophenolic acid, clavines (agroclavine and festuclavine), citreoisocoumarin, and orsellinic acid. In addition the biosynthesis of patulin (a P. paneum and P. carneum product) is discussed. Penicillium camemberti grows on the surface of Camembert, Brie, and related white rind cheeses, and the penetration of secondary metabolites inside the cheese is relevant. One of the P. camemberti metabolites, cyclopiazonic acid, is important because of its neurotoxicity and its biosynthesis is reviewed. The removal of toxic metabolites gene clusters by precise gene excision while preserving all other characteristics of the improved starter strains, including enzymes involved in cheese ripening and aroma formation, is now open. A possible strain improvement application to the cheese industry is of great interest.

The evolution of higher fungi and actinomycetes took place on solid growth substrates, so these microorganisms are perfectly adapted to grow in a solid environment. This implies that their cultivation in liquid culture may impair their metabolic efficiencies. However, conventional technology for the production of valuable fungal products is liquid submerged fermentation. In recent times, solid-state fermentation has become an alternative industrial production system to produce enzymes, primary and secondary metabolites. There are several advantages in employing many solid-state fermentation processes over the conventional submerged fermentation ones, like higher yields of secondary metabolites or enzymes. Moreover, certain enzymes and secondary metabolites can only be produced in solid-state fermentation. The main advantages of this culture system are related to the special physiology displayed by fungi when growing in solid culture. This chapter describes and analyzes recent advances in our understanding of this special physiology (the physiology of solid medium) and the underlying molecular mechanisms. It is also discussed how this knowledge can be applied to create novel technological advances.

Fungi produce extensive set of enzymes to degrade lignocellulosic plant biomass. Fungal (hemi)cellulases are among the most widely exploited microbial enzymes for many industrial and environmental applications. However, in biofuel industries and few other sectors, the cost of the enzymes is a big hurdle in the development of successful technology. So far industrial production of (hemi)cellulases is mainly achieved by submerged fermentation technique. But solid state fermentation (SSF) is an alternative low-cost and less energy-intensive technology which can lead to reduction in the cost of these enzymes. The chapter initially describes structure and occurrence of plant cellulose and hemicellulose and their degradation by fungal enzymes. Extracellular multienzyme systems of wood-rotting fungi, plant-pathogenic fungi, and thermophilic fungi are also reviewed. Production of (hemi)cellulases by SSF is explained with discussion on critical factors affecting the process and their optimization. Additionally, attempts to develop large-scale SSF processes using bioreactors are also described. Improvements of fungal (hemi)cellulases by genetic approaches and the current applications of (hemi)cellulases along with bioconversions of lignocellulosic waste into valuable products for use as energy source or food additives are briefly narrated.

Nanoparticles are structures in nanoscale with a wide range of applications across various fields of technology, industry, environment, medicine, and science. Increasing demands for NPs caused to develop their production based on chemical and physical approaches, recently. These approaches carry health and environmental disadvantages with themselves. Need for safer alternatives in large-scale production of NPs ended up with development of eco-friendly methods. Industrial nanobiotechnology takes advantage of biological-based approaches to produce nanomaterial using biological renewable resources. Decreasing energy intake, greenhouse gas (GHG), and hazardous waste production are the main advantages of nanomaterial biosynthesis. In contrast, the other synthesis methods bring environmental drawbacks. Among the nanomaterials, nanoparticles have attracted the attention because of their wide spectrum of application. Microorganisms and in particular bacteria and fungi are used as the biological agents and showed a promising potential for biosynthesis of nanoparticles. Here we highlight different aspects of industrial production of NPs by fungi including advantages and disadvantages. Also, we discuss the application of different technologies in development of high-scale production of NPs by fungi-like protein engineering, metabolic engineering, synthetic biology, systems biology, and downstream processing.

Marine fungi have been a rich source of bioactive natural products with interesting pharmaceutical activities and potential therapeutic applications. This chapter reviews the recent analytical techniques for discovery and the characterization of bioactive compounds derived from marine fungi, which are highly diversified and are less explored. An overview about bioprospecting, collection, preparation, and preservation of fungi samples are also presented, as well as different methods and strategies used for extraction, fractionation, and structural characterization of the bioactive compounds are discussed, including their advantages and the disadvantages. Possible roles of these natural compounds in several interesting biological activities are also covered in this chapter.

Over the past 10 years, we have intensively investigated the potential of the white-rot fungus Physisporinus vitreus for engineering value-added wood products. Because of its exceptional wood degradation pattern, i.e., selective lignification without significant wood strength losses and a preferential degradation of bordered pit membranes, it is possible to use this fungus under controlled conditions to improve the acoustic properties of resonance wood (i.e., “mycowood”) as well as to enhance the uptake of preservatives and wood modification substances in refractory wood species (e.g., Norway spruce), a process known as “bioincising.” This chapter summarizes the research that we have performed with P. vitreus and critically discusses the challenges encountered during the development of two distinct processes for engineering value-added wood products. Finally, we peep into the future potential of the bioincising and mycowood processes for additional applications in the forest and wood industry.

Lactones are important secondary metabolites for fungi. In this chapter are presented some lactones that are important in biotechnology such as flavoring lactones or fragrance macrocyclic musk compounds, whereas others are important for quorum sensing and health (mycotoxins). Different pathways or enzymes can give rise to lactones, and the pathways going through β-oxidation and ω-oxidation and the fungal polyketide pathway (relatively similar to the fatty acid synthesis pathway) are presented as well as the activity of Baeyer–Villiger monooxygenases and lactonases and their potential use in biotechnology.

With the impact of globalization on research trends; the search for healthier lifestyles; the increasing public demand for natural, organic, and “clean labelled” products; as well as the growing global market for natural colorants in economically fast-growing countries all over the world, filamentous fungi started to be investigated as readily available sources of chemically diverse pigments and colorants. The formulation of recipes containing fungal pigmented secondary metabolites has steadily increased over recent years. For all of these reasons, this chapter highlights exciting findings, which may pave the way for alternative and/or additional biotechnological processes for industrial applications of fungal pigments and colorants. The fungal biodiversity from terrestrial and marine origins is first discussed as potential sources of well-known carotenoid pigments (e.g., β-carotene, lycopene) and other specific pigmented polyketide molecules, such as Monascus and Monascus-like azaphilones, which are yet not known to be biosynthesized by any other organisms like higher plants. These polyketide pigments also represent promising and yet unexplored hydroxy-anthraquinoid colorants from Ascomycetous species. The putative biosynthetic pathways of the carotenoids and polyketide-derivative colored molecules (i.e., azaphilones, hydroxyanthraquinones, and naphthoquinones) in pigment-producing fungal species are investigated herein. As an additional aspect, this chapter describes biotechnological approaches for improving fungal pigment production and identifying new clean opportunities for the future. Alternative greener extraction processes of the fungal colored compounds are also further explored. The current industrial applications along with their limits and further opportunities for the use of fungal pigments in beverage, food, pharmaceutical, cosmetic, textile, and painting areas are, then, presented.

Yeast had participated with humans in food fermentation since the production of wine and bread, more than 10,000 years of shared history. It is well understood that fungi diversity is still underestimated and that we are far from understanding its importance and potential impact in biotechnology. Flavor compounds as “secondary metabolism” are very sensitive to fermentation conditions and mixed cultures, and although we had experience an exponential development of molecular biology in the last 30 years, metabolomics is still in its infancy. It was demonstrated in recent years that increase strain and species yeast diversity in a fermentation system increases sensory complexity and chemical aroma compound diversity in the final fermented product. Flavor compounds had many key functions for yeast, such as for survival and dispersion strategies, pheromone and defense mechanisms, and “quorum sensing” mechanisms for cell communication. Humans had taken advantage of many of these functions to increase taste and food sensory pleasure for a more exigent consumer, a phenomenon called “yeast domestication.” We focus this chapter mainly in the recent discussed yeast synthetic pathways for the formation of phenylpropanoid and terpenoid aroma compounds.

In addition, we will emphasize the current knowledge that grape and wine microbiology research has contributed to understand how complex natural and inoculated yeast flora can affect flavor quality. The flavor phenotype concept and how to screen natural flora and develop consortia starters to innovate in food biotechnology are discussed.

The use of immobilized cell technology (ICT) is viewed as a promising biotechnological tool to achieve high volumetric productivities of yeast fermentation in bioindustry of alcoholic beverages. During this process a huge number of organic compounds are being formed as yeast secondary metabolites, among which volatile compounds, such as higher alcohols, esters, and vicinal diketones, are the most important flavoring compounds. The objective of this chapter is to summarize the knowledge on the origin of the flavor-active and nonvolatile compounds synthesized by yeast and to describe how the composition of the medium, culture strain, process conditions (temperature, aeration, etc.), bioreactor design, and other critical parameters influence the metabolic activities of yeast cultures. Despite the technological and economic advantages provided by ICT, commercialization of this technology experienced only limited success, mainly due to unpredictable effect of immobilization on yeast physiology. This chapter is an attempt to rationalize and make some conclusions about the impact of cell immobilization on yeast metabolism collected from empirical experiences in production of alcoholic beverages. The knowledge addressing this issue may be of particular benefit to the nascent bioflavor industry.

Lipases are enzymes with remarkable properties and catalytic versatility. These proteins are capable of catalyzing hydrolytic and synthetic reactions, allowing the production of different compounds. Aspergillus are important producers of lipases, since they are able to secrete large amounts of these proteins to the extracellular media. Several studies have reported the importance of fermentation parameters as well as genetic engineering of Aspergillus strains in order to improve lipase production. Different Aspergillus species secrete lipases with interesting characteristics such as thermostability, stability in a wide pH range, stability in organic solvents, and enantioselectivity toward the substrate. The obtainment of lipases with highlighted characteristics for use in industry is the main focus of several studies. Such lipases can be obtained with screening of Aspergillus strains, protein engineering, and immobilization of lipases that can frequently improve thermostability and enantioselectivity. Among the applications of lipases from Aspergillus, there are studies on the improvement of sensorial properties of different products in the food industry, compatibility with detergents for removal of fat stains from fabrics, and the obtainment of enantiopure pharmaceuticals.

Emerging viewpoints from contemporary research on terrestrial fungal metabolites provides an insight into their valuable insidious biological activity including cancer therapeutics. Some well-characterized fungal metabolites surprisingly display remarkable antitumor properties at preclinical and clinical trial stage. Although their underlying mechanism of action is still being investigated, overwhelming evidence points to their actions operationally targeting core regulatory pathways and enzymes dysregulated during pathogenesis of cancer. Some metabolites have progressed into clinical pipeline, while others preset unique window of opportunity to capitalize as lead compound for future synthesis of anticancer drug of translational relevance. This chapter presents a succinct preclinical and clinical perspective on a few select and structurally diverse fungal metabolites with supportive mechanism-based bioactivity deciphered against tumor cells and with the presumptive notion of their future development as novel synthetic analog. The metabolites included are: Phenylahistin, Palmarumycin CP-1, Rhizoxin, Epoxyquinol B, Fumagillin, Destruxin B, Cotylenin A, Myriocin, Cytochalasin E, Chaetocin, Apicidin, and Galiellalactone. None of these agents are currently being adopted for treatment of cancer, but with some metabolite analog compounds, clinical trials have been conducted to ensure clinical safety and efficacy. However, based on overwhelming precedence of preclinical and clinical anticancer activity, this new class of structurally diverse fungal metabolites may become an important source of anticancer lead molecules for use either as monotherapy or in combination with other drugs in fight against cancer.

Mycotoxins are toxic substances produced by fungi that contaminate various food and feedstuffs. There are about 100 different types of mycotoxins which are produced by a wide range of fungal species. The variety of their toxicity is linked to the diversity of their chemical structure. Amongst them, three biosynthesis origins are mostly studied: the polyketides (e.g., aflatoxins, fumonisins), the terpenes (e.g., trichothecenes), and the ergot alkaloids (e.g., ergotamine). In this chapter we present those biosynthetic origins and focus on the mycotoxins threatening human health. Their biosynthesis, producing fungi, toxicity, and regulation are succinctly presented. In the second part of the chapter, we focus our attention on fungal metabolites as a potential source of biocontrol, being antifungal, impacting both fungal growth and mycotoxins production and preventing mycotoxins biosynthesis. We finally conclude on the wide diversity of mycotoxins origins and the need to pursue the discovery of new fungal metabolites to counteract mycotoxins production.

The basidiomycete Agaricus subrufescens Peck, also known as the almond mushroom due to its particular flavor, became in a few years one of the most important culinary-medicinal cultivable mushrooms with potentially high added-value products and extended agronomical valorization. As other mushrooms, it produces metabolites of great interest as potential antioxidant defensive agents to reduce the oxidative damage caused by free radicals. The quality of raw mushrooms or extracts and yield in metabolites may vary with the genetic background of the mushrooms and the environmental conditions. This chapter uses A. subrufescens as a guideline for illustrating the diversity in radical scavenging activities and metabolites in edible fungi, how it can be studied, and how active molecules might be identified.

For thousands of years, natural products from medicinal mushroom are being used for the cure of different lethal diseases. Among the huge category of medicinal herbs, the genus Cordyceps is gaining special attention due to its broad spectrum of biological activity. Cordycepin, a nucleoside analogue, is the main bioactive ingredient of Cordyceps and known to mediate a variety of pharmacological effects. Many chemically modified cordycepin derivatives have been reported which have shown more potential therapeutic effects. With the advancement in fermentation techniques, it has been possible to produce the higher cordycepin product. The modern techniques enabled the researchers for an easy detection and extraction of cordycepin from fermentation medium. Being a nucleoside analogue, cordycepin can interfere with the DNA/RNA biosynthesis and acts as a potential candidate for the treatment of the dreadful diseases such as cancer. Besides, cordycepin have also been known to modulate a variety of signaling pathways involved in apoptosis, proliferation, metastasis, angiogenesis, and inflammation. This chapter will describe the chemistry, production, detection, and extraction strategies of cordycepin. In addition, variety of therapeutic applications of cordycepin with all possible molecular mechanisms of actions have also been summarized.

Cyclosporin A is a cyclic undecapeptide with a variety of biological activities including immunosuppressive, anti-inflammatory, antifungal, and antiparasitic properties. It is an extremely powerful immunosuppressant and is approved for the use in organ transplantation to prevent graft rejection in kidney, liver, heart, lung, and combined heart–lung transplants. As its role in transplantation surgery increases, the demand on industry for improved yields intensifies. For this reason, this chapter mainly focuses on enhanced production of cyclosporin A from microbes by different techniques.

Streptokinase is a fibrinolytic agent widely used in thrombosis. The clinical trials and experimental studies proved that the SK is a safe and inexpensive thrombolytic medicine compared with its homologues such as tissue plasminogen activator (t-PA), urokinase (UK), and other plasminogen activators. Increased risk and prevalence of thrombosis worldwide, demand for SK, low production yields in native strain, high purification, and other antigenicity toxins limit the usage of native SK. However, these inadequacies can be overcome by using genetic engineering technology to express SK gene (skc) in microbial host systems. This chapter addresses about the SK structure, mechanism of action, and recombinant SK expression in yeast and fermentation.

Secondary metabolites of the fungus Monascus include pigments, monacolins, and citrinin. This chapter summarizes the biosynthesis of these metabolites, their biological activities, as well as new methods of determination based mainly on chromatography and spectrophotometry. In addition, asexual and sexual reproduction, solid substrates and submerged liquid cultivation conditions, together with the use of this fungus in food biotechnology and condiments are described. Emerging topics such as methods in molecular biology of Monascus, based on recent genomic sequencing of M. purpureus, M. ruber, and M. pilosus, are also discussed.

Fungi constitute an enormous unexplored pool of protease inhibitors. Only a handful of fungal protease inhibitors have been exhaustively characterized, but they reveal great versatility and many unique features and novel types of inhibitory mechanisms. Small molecule and protein inhibitors of all catalytic classes of proteases have been identified in fungi, those that target serine proteases predominating. As important regulators of proteases, the function and potential applications of protease inhibitors are intimately connected with those of proteases they inhibit. In this chapter, both small molecule and protein protease inhibitors from fungi are described, including their biochemical characteristics, inhibitory mechanisms, and biological functions together with their potential for application in the fields of biotechnology, crop protection, and medicine.

Ergot alkaloids are indole derivatives produced by a wide range of fungi, being considered medically important because of their significant effect on the central nervous system of mammals, due to their structural similarity to neurotransmitters. They are also considered mycotoxins due to the severe toxic effects of ergot-contaminated grains on human and animal health. This chapter summarizes different aspects of ergot alkaloids concerning their chemistry, biosynthesis, and bioactivity, discussing the pharmacological activity as well as some important aspects related to their toxicity, occurrence, and regulations. Finally, an overview of analytical methods for the determination of ergot alkaloids is included, whereby high-performance liquid chromatography coupled to fluorescence or mass spectrometer detection are the most widely used methods, although other techniques such as capillary electrophoresis or immunoassays have also been reported.

Lanostanes are a group of tetracyclic triterpenoids derived from lanosterol. They have relevant biological and pharmacological properties, such as cytotoxicity, immunomodulation, and anti-inflammation. Some of them also have interesting effects on metabolism and anti-infectious properties. This review will compile chemical data, biological effects, and mechanisms on the most relevant lanostanoids isolated from fungi, such as those from Ganoderma lucidum, Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and other.

Kombucha, fermented black tea with symbiotic association of bacteria and yeast, has been claimed by its drinkers for several health benefits. Health benefits of kombucha tea are directly associated with the composition and the concentration of the biomolecules present in it. Being a product fermented by bacteria and yeast association, kombucha has very complex composition which has a range of components from tea plant, bacteria, yeast, and compounds produced during fermentation process. The compounds responsible for the claimed benefits of kombucha have not been explored due to its complexity. This chapter focuses on the metabolites of kombucha which have been reported.