Terpenoids: Recent Advances in Extraction, Biochemistry and Biotechnology

Terpenoids are a class of chemicals with over 50,000 individual compounds, highly diverse in chemical structure, founded in all kingdoms of life, and are the largest group of secondary plant metabolites. Also known as isoprenoids, their structure began to be elucidated between the 1940s and 1960s, when their basic isoprenoid building blocks were characterized. They play several basic and specialized physiological functions in plants through direct and indirect interactions. Terpenoids are essential to metabolic processes, including post-translational protein modifications, photosynthesis, and intracellular signaling. All terpenoids are built through C5 units condensed to prenyl diphosphate intermediates. The fusion of these C5 units generates short C15-C25, medium C30-C35, and long-chain C40-Cn terpenoids. Along with the extension of the chain, the introduction of functional groups, such as ketones, alcohol, esters and, ethers, forms the precursors to hormones, sterols, carotenoids, and ubiquinone synthesis. The biosynthesis of terpenoids is regulated by spatial, temporal, transcriptional, and post-transcriptional factors. This chapter gives an overview of terpenoid biosynthesis, focusing on both cytoplasmic and plastid pathways, and highlights recent advances in the regulation of its metabolic pathways.

Terpenoids, also called isoprenoids or terpenes, are a large class of natural products which display a wide range of biological activities. They are major constituents of essential oils produced by aromatic plants and tree resins. Due to their notable biological activities, these compounds have enormous economic importance, being widely used as bioactive ingredients in the food, cosmetic, and pharmaceutical industries. The growing demand from consumers and regulatory agencies to develop green sustainable industrial processes has resulted in the emergence of new technologies for obtaining bioactive compounds from natural sources. Thus, many works have been reported in the literature regarding the development and application of new methods for obtaining terpenoids from natural sources that meet the demands of green processes, with reduced consumption of solvent and energy, less waste generation, and use of non-toxic solvents. This chapter proposes to present the main methods of green extraction to obtain terpenoids-rich extracts, with an emphasis on low-pressure methods, such as microwave-assisted extraction (MAE) and ultrasoundassisted extraction (UAE); and high-pressure methods (here considered as pressures greater than 5 bar), including extraction with supercritical fluids (SFE), subcritical water (SWE) and liquefied petroleum gas extraction (LPG). In addition, the future perspectives and the main challenges regarding the development of alternative methods for the recovery of terpenoids are presented and discussed.

Endophytic fungi are fungi that live inside plant tissues at any moment of their life cycle without causing damage or disease symptoms to their hosts. These microorganisms are producers of important substances with several biological activities. Terpenoids are one of the main classes of natural products produced by endophytic fungi, and have a wide range of biological activities, such as antiinflammatory, anticancer, antioxidant, antifungal, antimicrobial, anticholinesterase, antidepressant, antipyretic, antimalarial, among others. Brazil has one of the largest plant reserves on the planet, consisting of an almost untapped source of endophytic fungi. Thus, in this review chapter, we present the results of the research work of Brazilian researchers, with a focus on the isolation and identification of secondary metabolites of the terpenoid class produced by endophytic fungi and their biological activities. The review period includes January 2015 and June 2021.

Terpenes are compounds derived from the secondary metabolism of plants, which act biologically in several functionalities, fighting several predators such as fungi and bacteria. Monoterpenes and sesquiterpenes are some of the main compounds that characterize the chemical composition of essential oils. However, this concentration depends on several factors, such as the type of ecosystem, climate, temperature, and other circumstances that can directly impact the chemical composition of essential oil. The Myrtaceae family is considered one of the main families of Brazilian flora and presents a wide diversity of species. Within this family, some species produce essential oils rich in terpenoids, which, besides being responsible for some biological activities, have contributed to the expansion and search for new natural bioactive substances present in such volatile substances. Given the above, this chapter presents a literature search with current studies that prove the biological and antioxidant activities of terpenoids present in essential oils of species of the Myrtaceae family.

Annonaceae includes 2,106 species. Some species of this family have an economic interest in the international fresh fruit market and are often used as raw materials for cosmetics, perfumes and folk medicine. The most cited species are mainly those belonging to the genera Annona, Guatteria and Xylopia. Chemical investigations indicate that the characteristic constituents of the Annonaceae are terpenoids, including mono and sesquiterpenoids, such as α-pinene, β-pinene, limonene, (E)-caryophyllene, bicyclogermacrene, caryophyllene oxide, germacrene D, spathulenol and β-elemene. Antimicrobial, antioxidant, larvicidal, antiproliferative, trypanocidal, antimalarial and anti-inflammatory effects have been described in these terpenes. This work is an overview of the chemical properties and biological effects of the volatile terpenoids from Annonaceae species.

Substances used as repellents to avoid contact with ticks and tickborne disease are essential to control. Several compounds have been developed throughout human history to promote repellent activity, and in the last decades, synthetic repellents have been widely used. However, several humans, animal, and environmental health problems have been related to synthetic compounds. The use of natural molecules with low toxicity becomes an alternative to replace these compounds. The natural terpenoids from secondary plant metabolites are an essential group with repellency activity on different arthropods. This chapter addresses the primary terpenes with repellency activity, briefly identifying the effectiveness of tick repellents, test methodology, primary terpenes tested, and activity. The evaluated compound showed good repellent activity on different tick species and stages. However, through this chapter, we show the variations in the techniques used to evaluate the bioprospection of terpenes with possible repellent activity and a lack of in vivo repellency studies with terpenes. Finally, we emphasize the repellent activity of terpenes to encourage the use of natural compounds as a strategy to control ticks

Gastrointestinal nematodes affect the animal's health and cause economic losses in meat, milk, and wool production. Essential oils and their terpenoids have been shown to effectively control gastrointestinal nematodes and may be an alternative to control gastrointestinal nematodes. The great advantage of terpenoids is the possibility of acting on the parasite in a multidirectional way on the neuromuscular system and body structures of nematodes. The current chapter describes the pharmacological basis of the combination of terpenes and synthetic anthelmintics as an alternative for increasing antiparasitic efficacy. It is necessary to evaluate if these combinations show antagonist, additive or synergic effects at the pharmacokinetic and pharmacodynamic levels. The physicochemical properties, pharmacokinetic features and potential drugdrug interactions at the metabolism or transport level of monoterpenes may be relevant for obtaining effective concentrations against different nematodes. In this context, the prediction of absorption, distribution, metabolism and excretion (ADME) is essential to optimize the anthelmintic action of these compounds. The rapid absorption and elimination of monoterpenes after their oral administration may directly influence the drug concentration level attained at the target parasites and the resultant pharmacological effect. Therefore, investigations on the dose schedule, administration route and type of pharmaceutical formulation are necessary. The integration of in vitro assays, in silico analysis, and in vivo pharmaco-parasitological studies are relevant to corroborate the kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics

 Soil is a complex and dynamic system in constant change due to its natural processes, as well as interaction among physical, chemical and biological characteristics that take part in it. However, the greatest transformation occurred due to the farm business and the adopted management system. Thus, man can manipulate some soil characteristics and make it more suitable for cropping development. Although anthropic action cannot fully control how soil characteristics interact, it is possible to track them. The action of chemical substances should not be disregarded, a product of the secondary metabolism of plants, since they interfere with plant's ability to compete and survive. Such substances can act out as protectors against herbivores and pathogens. They can be attractive or repellent agents in plant-plant competition and plant-microorganism symbiosis. They can also influence the interaction between plant matter and soil organisms. Among these substances, terpenoids are highlighted as the most structurally diverse chemical family in the class of secondary metabolites that are part of natural products. This knowledge allows a better understanding of nutrient decomposition and cycling processes, the influence of environmental factors on production and terpenoid variability in some plants with medicinal and economic importance. 

Invasive plants represent a source of economic damage to the agricultural system, and their management has become indispensable from an agronomic point of view, as such plants are known for their competitiveness for resources such as water, light, nutrients, and space. Their control is performed in some cases, such as in Brazil, through the use of pesticides, which can be harmful to human health and other animals. With the change of habits and the search for a better quality of life, the use of these chemicals in management areas is increasingly less encouraged. A possible ecological alternative would be the use of natural products, as secondary metabolites have been shown as potential promoters of phytotoxic activity. Among the allelochemicals produced naturally, terpenoids can be highlighted because their chemical variability can help in the sustainable management of invasive plants. 

 Food additives are widely used in the food industry in order to ensure the quality of products during processing, storage, packaging and subsequent reaching the consumer's table. The growing concern and doubt of the consumer market regarding artificial additives and their possible harmful effects on public health and safety have caused the demand for the use of natural additives to increase. Consequently, these natural additives have been increasingly sought by the food industry and consumers due to health, safety and sustainability issues. In this framework, terpenoids have great potential to be used with this function because they are a very extensive class of compounds, with wide chemical diversity and several proven applications in foods, mainly as anti-oxidants, anti-microbials, dyes, flavors, sweeteners and nutraceuticals. Therefore, this paper aims to make a literature search on the use of terpenoids as food additives, highlighting the main compounds used and the benefits associated with their use, ranging from the raw material to its extraction and subsequent application in food products.

Essential oils (EOs) have diverse chemical compositions depending on the plant species used, but the most common constituents present in EOs are mono- and sesquiterpenoids. Such volatile terpenoids have different functions in plant ecology, acting, for example, as chemical defenses against fungi, bacteria, and insects, attracting pollinators, inhibiting germination, and mediating intra- and interspecific plant communication. Mainly terpenoids present the ability to inhibit the main families of detoxifying enzymes of insects, allowing the formulation of botanical insecticides, and using blends of EO compounds considered synergists among themselves. In this case, both combinations of essential oils from different plants and the enrichment of essential oils and/or their fractions with compounds with proven synergistic effects can be considered. This chapter presents research results that indicate synergistic, additive, and antagonistic interactions between terpenoids, indicating that this is one of the main properties considered when formulating insecticides based on commercially available EOs. Considerable advances are still necessary for large-scale production, and limitations related to raw material supply, registration, and, mainly, adequacy of formulations for the control of different targets without phytotoxic effects, are the main challenges to be overcome in the short-term

The antimicrobial effect of essential oils and their main constituents, the terpenoids, has been generally reviewed in this article, with a comparative investigation of the structure-activity relationship. Terpenoids are widespread metabolites in plants belonging to different chemical classes, whereas oxygenated derivatives constitute the predominates. They could be classified as diterpenes, triterpenes, tetraterpenes, or hemiterpenes and sesquiterpenes. As crude materials, terpenoids are also broadly utilized in drug, food, and beauty care product ventures. Terpenoids have antitumor, anti-inflammatory, antibacterial, antiviral, antimalarial effects, promote transdermal absorption, prevent and treat cardiovascular diseases, and hypoglycemic activities. Moreover, terpenoids have many critical uses as insecticides, immunoregulators, antioxidants, antiaging, and neuroprotection agents. Terpenoids have a complicated construction with assorted impacts and various components of activity. Using plants – containing – terpenoids as neutraceuticals in the nutrition of humans and animals also constitutes a potential issue as natural inhibitors for microbes. These phytochemicals are generally conveyed in soil products and are particularly helpful in food protection as microbial development inhibitors. 

Propolis is a resin, which comes from from bee colonies and is considered a natural antibiotic, without serious side effects, compared to synthetic treatments, and has several pharmacological properties. Geopropolis is a mixture of clay and propolis produced by species of stingless bees of the genus Melipona, hence the name geopropolis. It is formed in the same way as propolis produced by other bee species. In this review, we aim to address general aspects related to terpenoids present in propolis and geopropolis. Here, we report the main terpenoids, their chemical structure, and pharmacological and food industry applications

Terpenoids, or isoprenoids, represent a large and structurally diverse class of isoprene-based secondary metabolites that play a fundamental role in the organism of all living beings. In nature, terpenes are essential for the interaction of organisms with their environment, mediating antagonistic and beneficial interactions between organisms. In this chapter, we will cover the biotechnology production of terpenes, as well as their biosynthesis by micro-organisms. We will also investigate the various pharmaceutical applications of these compounds.