Prostaglandins in Marine Organisms: A Review

Costanzo, F. Di; Dato, Valeria Di; Ianora, Adrianna; Romano, Giovanna

doi:10.3390/md17070428

Cited by 68 publications

(50 citation statements)

References 110 publications

(151 reference statements)

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“…synthases 7 , respectively. Depending on which precursor is used, three series of PGs are produced, each having its own receptor series whose binding determine the type of message transduced 8 .…”

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confidence: 98%

Variation in prostaglandin metabolism during growth of the diatom Thalassiosira rotula

Dato

Barbarinaldi

Amato

et al. 2020

Sci Rep

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prostaglandins (pGs) are hormone-like mediators in many physiological and pathological processes that are present in all vertebrates, in some terrestrial and aquatic invertebrates, and have also been identified in some macroalgae. They have recently been reported also in marine microalgae but their role as chemical mediators is largely unknown. Here we studied the expression pattern of the PG biosynthetic pathway during different growth phases of the centric diatom Thalassiosira rotula and assessed the release of PGs in the surrounding environment for the first time. We show that enzymes responsible for PGs formation such as cyclooxygenase, prostaglandin E synthase 2-like and prostaglandin F synthase are mainly expressed at the end of the exponential phase and that PGs are released especially during the stationary and senescent phases, suggesting a possible signaling function for these compounds. Phylogenetic analysis of the limiting enzyme, COX, indicate the presence in diatoms of more than one enzyme related to the oxidative metabolism of fatty acids belonging to the peroxidase-cyclooxygenase superfamily. These findings suggest a more complex evolution and diversity of metabolic pathways leading to the synthesis of lipid mediators in diatoms. Arachidonic acid (ARA), eicosapentaenoic acid (EPA), eicosatrienoic acid (ETrA) and docosahexaenoic acid (DHA) are polyunsaturated fatty acids that are physiologically important for animals at all taxonomic levels, including humans. EPA and DHA contribute to the healthy functioning of the cardiovascular system 1 and are precursors of important classes of fatty acid-derivatives playing multiple signaling roles in inflammation and immune responses, platelet aggregation and tumor growth 2,3. Among these, the inflammation process is one of the most important mechanisms adopted by organisms in response to various external stimuli 3. Inflammation involves a complex interplay of signaling molecules whose final goal is to restore the healthy status of a cell or tissue. Consequences of sustained inflammation are indeed the development of serious diseases such as cancer and autoimmune disorders 4. Included in the eicosanoids are prostaglandins (PGs) synthesized principally from arachidonic acid (ARA) in animals, but also from EPA and ETrA, through the enzymatic route initiated by cyclooxygenase (COXs) enzymes 5. PGs are molecules with a hormone-like behavior playing a prominent role in many physiological processes that have been principally studied in animals 3. The expression of the COXs enzymes is mandatory for their synthesis. COXs exist in two isoforms that differ for their subcellular localization and for their expression timing. COX-1 is located in the endoplasmic reticulum and is constitutively expressed at constant levels in many tissues unless external cues, such as tumor promoting factor, cytokine and growth factor, induce an increase in its expression level. COX-2 is the inducible form, which is not detectable unless a trigger similar to those that stimulate COX-1 express...

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confidence: 98%

Variation in prostaglandin metabolism during growth of the diatom Thalassiosira rotula

Dato

Barbarinaldi

Amato

et al. 2020

Sci Rep

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“…Studies on the evolutionary relationships of the diatom COX protein sequence with those from other organisms, showed similarity between diatom and animal COXs. Alignment of the diatom and human sequences denoted a 29% identity and a dendrogram construction showed the clustering of the diatom and human COX sequences in sister clades [15]. The above results indicate the conservation of the biosynthetic pathway for these mediators among the different kingdoms of life, suggesting an important ecological and functional role also in simple organisms.…”

Section: Introductionmentioning

confidence: 64%

“…Different types of Pgs have been discovered also in marine organisms but their role in the marine environment still awaits to be discovered [15].…”

Section: Discussionmentioning

confidence: 99%

“…While their involvement in the physiology of terrestrial organisms have been extensively studied, in marine organisms only scattered studies exist that have established their presence but not yet their function [15]. Very recently, the synthesis of Pgs have been investigated in phytoplanktonic organisms, such as marine diatoms [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…Enzymes involved in the pathway are reported as underlined text next to the arrows. For the abbreviation, refer to the text (Modified from Di Costanzo et al 2019[15]).…”

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Identification of Prostaglandin Pathway in Dinoflagellates by Transcriptome Data Mining

2020

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Dinoflagellates, a major class of marine eukaryote microalgae composing the phytoplankton, are widely recognised as producers of a large variety of toxic molecules, particularly neurotoxins, which can also act as potent bioactive pharmacological mediators. In addition, similarly to other microalgae, they are also good producers of polyunsaturated fatty acids (PUFAs), important precursors of key molecules involved in cell physiology. Among PUFA derivatives are the prostaglandins (Pgs), important physiological mediators in several physiological and pathological processes in humans, also used as “biological” drugs. Their synthesis is very expensive because of the elevated number of reaction steps required, thus the search for new Pgs production methods is of great relevance. One possibility is their extraction from microorganisms (e.g., diatoms), which have been proved to produce the same Pgs as humans. In the present study, we took advantage of the available transcriptomes for dinoflagellates in the iMicrobe database to search for the Pgs biosynthetic pathway using a bioinformatic approach. Here we show that dinoflagellates express nine Pg-metabolism related enzymes involved in both Pgs synthesis and reduction. Not all of the enzymes were expressed simultaneously in all the species analysed and their expression was influenced by culturing conditions, especially salinity of the growth medium. These results confirm the existence of a biosynthetic pathway for these important molecules in unicellular microalgae other than diatoms, suggesting a broad diffusion and conservation of the Pgs pathway, which further strengthen their importance in living organisms.

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Prostaglandin production by the microalga with heterologous expression of cyclooxygenase

Maeda

Tsuru

Matsumoto

et al. 2021

Biotech & Bioengineering

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Prostaglandins (PGs) are the physiologically active compounds synthesized from C20 polyunsaturated fatty acids (PUFAs) by cyclooxygenase (COX) and a series of PG synthases, and are utilized as pharmaceuticals. Currently, commercialized PGs are mainly produced by chemical synthesis under harsh conditions. By contrast, bioproduction of PGs can be an alternative, environmental-friendly, and inexpensive process with genetic engineering of model plants, although these conventional host organisms contain a limited quantity of PG precursors. In this study, we established an efficient PG production process using the genetically engineered microalga Fistulifera solaris which is rich in C20 PUFAs. A cox gene derived from the red alga Agarophyton vermiculophyllum was introduced into F. solaris. As a result, a transformant clone with high cox expression produced PGs (i.e., PGD 2 , PGE 2 , PGF 2α , and 15-ketoPGF 2α derived from arachidonic acid, and PGD 3 , PGE 3 , and PGF 3α derived from eicosapentaenoic acid) as revealed by liquid chromatography/mass spectrometry. The total content of PGs was 1290.4 ng/g of dry cell weight, which was higher than that produced in the transgenic plant reported previously.The results obtained in this study indicate that the C20 PUFA-rich microalga functionally expressing COX is a promising host for PG bioproduction.

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Prostaglandins in Marine Organisms: A Review

Cited by 68 publications

References 110 publications

Variation in prostaglandin metabolism during growth of the diatom Thalassiosira rotula

Variation in prostaglandin metabolism during growth of the diatom Thalassiosira rotula

Identification of Prostaglandin Pathway in Dinoflagellates by Transcriptome Data Mining

Prostaglandin production by the microalga with heterologous expression of cyclooxygenase

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