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inequalityGoal 11: Sustainable cities and communitiesGoal 12: Responsible consumption and productionGoal 13: Climate actionGoal 14: Life below waterGoal 15: Life on landGoal 16: Peace, justice and strong institutionsGoal 17: Partnership for the goalsAreasSocial sciencesMathematics and physicsChemistryEngineering sciencesInformaticsBiological sciencesAgriculture and EnvironmentMedicine, dentistry and pharmacologyHumanitiesEventsEventsEvent categoriesTalksOpen lecturesUniversity activitiesEvent areasSocial sciencesEvent locationsRokkodai 1st CampusOff-campusOnlineEvent audiencesStudentsAudienceProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staff CloseNews TopCategoriesPress releasesRead in日本語2019.12.13Success in metabolically engineering marine algae to synthesize valuable antioxidant astaxanthin Engineering sciencesBiological engineeringMetabolomic analysisAlgaeCyanobacteria (blue-green algae)A research group led by Professor HASUNUMA Tomohisa of Kobe University’s Engineering Biology Research Center have succeeded in synthesizing the natural pigment astaxanthin using the fast-growing marine cyanobacterium Synechococcus sp. PCC7002.This process required light, water and CO2 to produce the valuable antioxidant astaxanthin from the cyanobacterium host at a faster rate and with lower contamination risks than previous methods of biologically synthesizing this useful substance. In addition, dynamic metabolic analysis revealed that astaxanthin production enhances the central metabolism of Synechococcus sp. PCC7002.It is hoped that these developments could be utilized to meet the demand for natural astaxanthin in the pharmaceutical and nutritional industries, amongst others, in the future.The results of this study were first published in the international journal ‘ACS Synthetic Biology’ on October 25 2019.IntroductionCarotenoids are pigments found in nature- the most well-known being the orange β-carotene (beta-carotene), which is found in carrots among other vegetables, fruits and plants. Various studies on different carotenoids have suggested that they can protect against cancers, premature aging and degenerative diseases.Astaxanthin (pink carotenoid) is the strongest antioxidant among known carotenoids. It is used as a natural coloring in aquaculture, cosmetic, nutrition and pharmaceutical industries among others, due to its enhancement of immune responses and anti-inflammatory properties. For example, it is utilized as an additive in chicken and fish feed.Currently, the majority of commercial astaxanthin is chemically synthesized from petrochemicals. This enables large amounts to be produced in order to meet demand. However, there are concerns about the safety of consuming astaxanthin synthesized from petrochemicals, and as a result the demand for natural astaxanthin is increasing.Research BackgroundThe freshwater alga Haematococcus pluvialis produces astaxanthin naturally and is responsible for the pink spots of astaxanthin commonly seen in birdbaths. For commercial astaxanthin production, Haematococcus requires a complex 2-stage process (Figure 1, top). After the first growth stage, Haematococcus is placed under inductive stress conditions such as nitrogen starvation or high light irradiation. This induces the plant to form hematocysts and produce astaxanthin in the second stage. However the slow growth in the first stage and subsequent cell deterioration in the second stage increase the risk of contamination. Furthermore, high light irradiation extrapolates production costs.Consequently, current methods of producing natural astaxanthin are not commercially viable enough for large-scale production. It is hoped that this powerful antioxidant carotenoid could be further utilized for human consumption in the nutrition and pharmaceutical industries if more efficient ways of producing it biologically are developed.The current study sped up the growth rate and reduced the contamination risks in biosynthesizing astaxanthin. The researchers succeeded in producing astaxanthin using the fast-growing marine blue-green algae species, or cyanobacterium, Synechococcus sp. PCC7002 as a host. This algae does not inherently produce astaxanthin, however by integrating β -carotene encoding genes into the Synechococcus, the expressed genes only require water, light and CO2 in order to produce astaxanthin.  This single stage method (Figure 1, bottom) does not require subjecting the cells to stress conditions and enabled astaxanthin to be produced in a shorter time period compared to the Haematococcus method. In addition, it is proposed that the rich salt concentration in Synechococcus could also lower the risk of contamination.Figure 1: Methods of biologically synthesizing astaxanthin:Two stage batch process using Haematococcus pluvialis (above) and this study’s single stage process using Synechococcus sp. PCC 7002 (below).Research MethodologyFigure 2: Visual comparison between the control strain and the astaxanthin-producing strains of Synechococcus.As previously mentioned, Synechococcus sp. PCC7002 does not inherently produce astaxanthin. Therefore it was necessary to take the encoding genes for β-carotene hydroxylase and β-carotene ketolase from the marine bacterium Brevundimonas sp. SD212 and integrate them into the Synechococcus. The genes were then expressed to biosynthesize astaxanthin. The host Synechococcus sp. PCC7002 was then able to produce astaxanthin via photosynthesis under a stress-free level of light similar to natural sunlight. As shown in Figure 2, the production of pink astaxanthin makes the solution turn a darker green color.This study is thought to be the first in the world to succeed in producing astaxanthin utilizing this particular marine cyanobacterium. With CO2 as the sole carbon source, this modified strain of Synechococcus sp. PCC7002 yielded 3mg/g dry cell weight astaxanthin, a production speed of 3.35mg/L/day. This is believed to be highest rate achieved so far using green algae.A dynamic metabolic profiling method developed by Professor Hasunuma et al. was used to analyze the metabolics inside the cells during astaxanthin production. This analysis revealed an increase in fractions of phosphates- in particular deoxyxylulose 5-phosphate (DXP), glyceladehyde 3-phosphate (GAP); and methylerithritol 4-phosphate (MEP). Furthermore, the level of the intermediary deoxyxylulose 5-phosphate (DXP) in the nonmevalonate pathway (a precursor metabolic pathway for astaxanthin production) also increased (Figure 3). In vivo C-labelling revealed that the carbon flow in the central metabolism was enhanced by the expression of the β-carotene encoding genes.These results indicate that astaxanthin producing cells are active in the initial metabolic stage. The reason for this is believed to be due to the cyanobacteria enhancing its central metabolism and the nonmevalonate pathway in order to try to replenish pigments such as β-carotene that are being used to synthesize the astaxanthin. In other words, astaxanthin production enhances the central metabolism of Synechococcus sp. PCC7002 to compensate for the lack of light harvesting pigments.It is hoped that further metabolic pathway engineering could reduce potential bottlenecks and further increase astaxanthin production.Figure 3: Estimated metabolic changes induced by astaxanthin production.Further ResearchOverall, this study showed that the modified Synechococcus sp. PCC7002 is a promising host for producing astaxanthin biologically through photosynthesis. This could be investigated further by trying to synthesize various other useful substances utilizing Synechococcus sp. PCC7002.In addition, it is hoped that the dynamic metabolic profiling method developed during this research could be utilized to improve understanding of metabolic processes in microorganisms, plants and animals.Journal InformationTitle“Single-stage astaxanthin production enhances the non-mevalonate pathway and photosynthetic central metabolism in Synechococcus sp. PCC 7002”DOI10.1021/acssynbio.9b00280AuthorsTomohisa Hasunuma, Ayako Takaki, Mami Matsuda, Yuichi Kato, Christopher John Vavricka, Akihiko KondoJournalACS Synthetic BiologyAccess at the Kobe University Repository KernelRelated linkBioProduction Engineering LabResearchersHasunuma TomohisaProfessorEngineering Biology Research CenterKATO YuichiAssistant ProfessorEngineering Biology Research CenterVavricka ChristopherGraduate School of Science, Technology and InnovationKondo AkihikoProfessorGraduate School of Science, Technology and InnovationSDGs)">)">Engineering Biology Research CenterGraduate School of Science, Technology and InnovationSHAREMore from these researchersInterviews2023.02.20Engineering sciencesBioengineering to Achieve Carbon NeutralityPress releases2022.07.08Engineering sciencesBioproduction Breakthrough: New method for developing Pichia pastoris yeast strains with high productivity of useful proteinsPress releases2022.06.10Engineering sciencesTyrosine chassis for sustainable, high-yield production of useful compounds in yeast smart cellsPress releases2022.04.13Engineering sciencesDiscovery of new phenomenon a game-changer for efficient bioproduction of useful chemicalsMore about these topicsPress releases2020.03.10Engineering sciencesSuccessful method yielding high rate of D-lactate using cyanobacteria could revolutionize bioplastic productionPress releases2018.06.06Engineering sciencesWorld’s most efficient production of succinate from carbon dioxidePress releases2017.04.17Engineering sciencesMaking oil from algaePress releases2021.05.06Engineering sciencesMicroalgae biofuelsページの先頭へ1-1, Rokkodai-cho, Nada-ku, Kobe, 657-8501, JAPANProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staffContactAccessJobsOfficial social media accountsCampus calendarPrivacy policySite policySite map© Kobe University

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