Journal of Medicinal Plants A Review on Biosynthesis, Health Benefits and Extraction Methods of Fucoxanthin, Particular Marine Carotenoids in Algae Irvani N (M.Sc.)1, Hajiaghaee R (Ph.D.)2, Zarekarizi A.R (M.Sc.)2* 1- Faculty of Biological Science and Technology, Shahid Beheshti University, Tehran, Iran 2- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran * Corresponding author: Institute of Medicinal Plants, ACECR, Karaj, Iran P.O.BOX (Mehr Vila): 31375-369 Tel: +98 - 26 – 34764010-18, Fax: +98 – 26- 34764021 E-mail: [email protected] Received: 28 June 2017 Accepted: 18 July 2018 Abstract Fucoxanthin, an allenic carotenoid, is abundant in macro and microalgae as a component of the light-harvesting complex for photosynthesis and photo protection. This carotenoid has shown important pharmaceutical bioactivity, exerting antioxidant, anti-cancer, anti-diabetic, anti- obesity, anti-photoaging, anti-angiogenic, and anti-metastatic effects on a variety of biological models. This carotenoid has been proven to be safe for animal consumption, opening up the opportunity of using this bioactive compound in the treatment of different pathologies. In this paper, an updated account of the research progress in biosynthetic pathway and health benefits of fucoxanthin is presented. Meanwhile, a review on the various methods of extraction of fucoxanthin in macro and microalgae is also revisited. According to these studies providing important background knowledge, fucoxanthin can be utilized into drugs and nutritional products. Keywords: Fucoxanthin, Carotenoids, Biosynthesis pathway, Extraction methods 6 Volume 17, No. 67, Summer 2018 … A Review on Biosynthesis Introduction million species [5]. Microalgae are important Consumer awareness of the importance of a primary producers in marine environments and healthy diet, protection of the environment, play a significant role in supporting aquatic resource sustainability and using all natural animals [6]. Mass production of microalgae resources are continuously increasing and can be carried out outdoors or indoors in fortunately enhance awareness among people bioreactors under optimal conditions [7]. This towards natural products due to their non-toxic makes microalgae a potentially sustainable properties, low pollution and less side effects source of feedstock for fuel, food, chemical, [1]. Microalgae (unicellular organisms) and textile, polymer and even the pharmaceutical macroalgae (multicellular organisms) belong industry [4]. to the large algae group made up of Carotenoids are tetraterpenoids with a photosynthetic organisms [2]. In recent characteristic linear C40 molecular backbone decade, there is a growing interest in using containing up to 11 conjugated double bonds, marine algae as an alternative food source. which are synthesized by all photosynthetic Marine algae are distributing from the polar organisms as well as by many non- region to tropical areas, range in size from photosynthetic bacteria and fungi [8]. There microscopic individual cells of microalgae to are two main classes of naturally occurring huge seaweeds and from nutrient-rich coastal carotenoids: carotenes, which are seas to oligotrophic open oceans [3]. hydrocarbons that are either linear orcyclized Algae have created enormous interest due at one or both ends of the molecule; and to their unconventional growth requirements xanthophylls which are oxygenated derivatives [4]. They provide an opportunity to exploit the of carotenes. In general, a distinction can be underutilized arable lands and oceans without made between primary and secondary reducing the agricultural production surface, carotenoids. Primary xanthophylls are defined which needs to be supplemented in order to as xanthophylls which are structural and feed the growing global population. Seaweeds functional components of the photosynthetic live in the coastal regions of ocean waters, apparatus of the cell and therefore essential for regularly within rocky intertidal or submerged cellular survival. Secondary xanthophylls are reef-like habitats. In this environment, a defined as xanthophylls that algae produce in nutrient struggling for light and space is fierce large quantities only after having been exposed and seaweeds have evolved chemical defense to specific environmental stimuli [9]. mechanisms to ward off predators and increase Fucoxanthin one of the major marine survival. Not surprisingly, many of these xanthophylls, occurs in some macro and chemicals are biologically active and some microalgae and has a unique structure including possess potent pharmacological activity [3]. an allenic bond, a conjugated carbonyl, a 5, 6- Furthermore, Marine microalgae constitute the monoepoxide and acetyl groups [10, 11] (Figure largest group of living organisms in the ocean 1). It serves as an antenna carotenoid in with an estimated range of 2×105 to several 7 Irvani & et al. Figure 1- Structure of Fucoxanthin the light-harvesting complexes where it is identification of biosynthesis pathway and coupled to the thylakoid membrane to transfer improvement of efficient extraction methods excitation energy to the photosynthetic are clearly necessary. Hence, this article electron transport chain via chlorophyll a [12, reviews the current available scientific 13]. Fucoxanthin has attracted considerable literature regarding the Biosynthesis, Health interest because of its potent bioactivities, Benefits and extraction methods of including its antioxidant, anti-inflammatory, fucoxanthin from macro and micro algae. anticancer, anti-obese, antidiabetic, antiangiogenic, and antimalarial activities, and Biosynthesis of fucoxanthin and Enzymatic its protective effects on the liver, blood vessels Reactions of the brain, bones, skin, and eyes [8, 14]. The Some common carotenogenesis genes in effects on adult T-cell leukemia cells, and algae are suggested from homology of the inhibitory effect on the viability of HL-60 cells known genes, but most genes and enzymes for of fucoxanthin are distinctly more potent than algae-specific pathways are still unknown. To that of β-carotene and astaxanthin [15]. This exploit our knowledge regarding this carotenoid has been proven to be safe for carotenoid in the medical fields and industrial animal consumption [16], opening up the applications, resolution of this pathway at the opportunity of using this bioactive compound molecular level is very important [8]. in the treatment of different pathologies [12]. Isopentenyl pyrophosphate (IPP), a C5- Though chemical synthesis of fucoxanthin is compound, is the source of isoprenoids, possible, it is very expensive and hence the terpenes, quinones, sterols, phytol of viability of obtaining directly from brown chlorophylls, and carotenoids. There are two seaweeds should not be overlooked [17]. known independent pathways of IPP synthesis: The promising prospect envisaged in this the classical mevalonate (MVA) pathway and new field of scientific collaboration arose our the alternative, non-mevalonate, 1-deoxy-d- interest to produce fucoxanthin. To perform xylulose-5-phosphate (DOXP) pathway. In the such grave attempt, an intensive work on MVA pathway, acetyl-Coenzyme A is 8 Journal of Medicinal Plants, Volume 17, No. 67, Summer 2018 … A Review on Biosynthesis converted to IPP through mevalonate. The precursor of fucoxanthin. The neoxanthin pathway is found in plant cytoplasm, animals hypothesis, on the other hand, proposes a and some bacteria [18, 19, 20]. In the DOXP branching of the pathway from neoxanthin to pathway, pyruvate and glycelaldehyde are both diadinoxanthin and fucoxanthin. The converted to IPP and the pathway is found in reasons for these differing hypotheses cyanobacteria, the plastids of algae, land plants regarding the fucoxanthin biosynthetic and some bacteria [9, 14]. pathways are: (1) that no pathway intermediate Farnesyl pyrophosphate (C15) is has been detected by HPLC, and (2) that the synthesized from three IPPs, after which, one genes encoding enzymes involved in the IPP is added to farnesyl pyrophosphate by biosynthesis of fucoxanthin have not been geranylgeranyl pyrophosphate synthase cloned [8]. (GGPS) to yield geranylgeranyl pyrophosphate For conversion of neoxanthin to (C20). In a head-to-head condensation of the fucoxanthin, two sequential reactions are two C20 compounds, the first carotene, necessary: ketolation of neoxanthin and phytoene (C40), is formed by phytoene acetylation of an intermediate [18]. Thus, synthase (Psy) using ATP. Four desaturation biochemical detection of the intermediate steps are needed in the conversion from which is probably fucoxanthinol, and phytoene to lycopene. Phytoene desaturase identification of genes encoding ketolase and (CrtP) catalyzes the first two desaturation acetylase are necessary to support the steps, from phytoene to ζ-carotene through neoxanthin hypothesis. phytofluene, and ζ-carotene desaturase (Zds) catalyzes two additional desaturation steps, Fucoxanthin Extraction from ζ-carotene to lycopene through An important factor determining the market neurosporene (Fig.2.). Lycopene is cyclized for fucoxanthin product development is the into β-carotene through γ-carotene [8, 14]. value of the target compound from the The biosynthetic pathway from organism of choice. The fucoxanthin β-carotenoid to violaxanthin is common to extraction efficiency was highly dependent on both diatoms and brown algae because genes the solvent type. Selecting the proper solvent encoding zeaxanthin epoxidase (ZEP) and to