The human intestinal microbiota that comprise over 1,000 species thrive in dark and anaerobic environments.They are recognized for the production of diverse low-molecular-weight metabolites crucial to human health and...The human intestinal microbiota that comprise over 1,000 species thrive in dark and anaerobic environments.They are recognized for the production of diverse low-molecular-weight metabolites crucial to human health and diseases.Carotenoids,low-molecular-weight pigments known for their antioxidative activity,are delivered to humans through oral intake.However,it remains unclear whether human intestinal bacteria biosynthesize carotenoids as part of the in-situ microbiota.In this study,we investigated carotenoid synthesis genes in vari-ous human gut and probiotic bacteria.As a result,novel candidates,the crtM and crtN genes,were identified in the carbon monoxide-utilizing gut anaerobe Eubacterium limosum and the lactic acid bacterium Leuconostoc mesenteroides subsp.mesenteroides.These gene candidates were isolated,introduced into Escherichia coli,which synthesized a carotenoid substrate,and cultured aerobically.Structural analysis of the resulting carotenoids re-vealed that the crtM and crtN gene candidates of E.limosum and L.mesenteroides mediate the production of 4,4′-diaponeurosporene through 15-cis-4,4′-diapophytoene.Evaluation of the crtE-homologous genes in these bacteria indicated their non-functionality for C40-carotenoid production.E.limosum and L.mesenteroides,along with the known carotenogenic lactic acid bacterium Lactiplantibacillus plantarum,were observed to produce no carotenoids under strictly anaerobic conditions.The two lactic acid bacteria synthesized detectable levels of 4,4′-diaponeurosporene under semi-aerobic conditions.The findings highlight that the obligate anaerobe E.limo-sum retains aerobically functional C30-carotenoid biosynthesis genes,potentially with no immediate self-utility,suggesting an evolutionary direction in carotenoid biosynthesis.(229 words)展开更多
The genus Algoriphagus comprises a group of red-colored,Gram-negative,aerobic bacteria that inhabit various marine environments.Several species of Algoriphagus produce the keto-monocyclic carotenoid flexixanthin;howev...The genus Algoriphagus comprises a group of red-colored,Gram-negative,aerobic bacteria that inhabit various marine environments.Several species of Algoriphagus produce the keto-monocyclic carotenoid flexixanthin;however,information on its derivatives and their biological activities is limited.In this study,Algoriphagus sp.strain Fs4 was isolated from the surface of seaweed collected at Nanaehama,Hokkaido,Japan.Based on structural analysis via nuclear magnetic resonance spectroscopy,of the carotenoid produced by the strain,it was identified as 2′-hydroxyflexixanthin,a new carotenoid in the genus Algoriphagus.A comparison of the carotenoid profiles of 25 species of Algoriphagus bacteria revealed that flexixanthin was present in all strains,and some strains also produced 2-or 2′-hydroxyflexixanthin.The biological activities of flexixanthin and its derivatives were evaluated in terms of their antioxidant and anti-inflammatory effects against macrophages.The degree of inhibitory effect on lipid peroxidation was in the order:2-hydroxyflexixanthin>2′-hydroxyflexixanthin>flexixanthin.Conversely,flexixanthin significantly inhibited lipopolysaccharide-induced interleukin-1βand-6,and nitric oxide synthase 2 mRNA expression,demonstrating a stronger inhibitory effect than that of 2′-hydroxyflexixanthin;2-hydroxyflexixanthin showed no significant inhibitory effects.These results indicate that the introduction of hydroxyl groups at specific sites affects the antioxidant and anti-inflammatory activities of flexixanthin.The findings of this study highlights the potential of the genus Algoriphagus as a source of flexix-anthin and its derivatives and provides a basis for the future application of these monocyclic carotenoids in the production of nutraceuticals and pharmaceuticals.展开更多
文摘The human intestinal microbiota that comprise over 1,000 species thrive in dark and anaerobic environments.They are recognized for the production of diverse low-molecular-weight metabolites crucial to human health and diseases.Carotenoids,low-molecular-weight pigments known for their antioxidative activity,are delivered to humans through oral intake.However,it remains unclear whether human intestinal bacteria biosynthesize carotenoids as part of the in-situ microbiota.In this study,we investigated carotenoid synthesis genes in vari-ous human gut and probiotic bacteria.As a result,novel candidates,the crtM and crtN genes,were identified in the carbon monoxide-utilizing gut anaerobe Eubacterium limosum and the lactic acid bacterium Leuconostoc mesenteroides subsp.mesenteroides.These gene candidates were isolated,introduced into Escherichia coli,which synthesized a carotenoid substrate,and cultured aerobically.Structural analysis of the resulting carotenoids re-vealed that the crtM and crtN gene candidates of E.limosum and L.mesenteroides mediate the production of 4,4′-diaponeurosporene through 15-cis-4,4′-diapophytoene.Evaluation of the crtE-homologous genes in these bacteria indicated their non-functionality for C40-carotenoid production.E.limosum and L.mesenteroides,along with the known carotenogenic lactic acid bacterium Lactiplantibacillus plantarum,were observed to produce no carotenoids under strictly anaerobic conditions.The two lactic acid bacteria synthesized detectable levels of 4,4′-diaponeurosporene under semi-aerobic conditions.The findings highlight that the obligate anaerobe E.limo-sum retains aerobically functional C30-carotenoid biosynthesis genes,potentially with no immediate self-utility,suggesting an evolutionary direction in carotenoid biosynthesis.(229 words)
基金supported by JSPS KAKENHI(21H02276 and 23K14018)and J-PEAKS.
文摘The genus Algoriphagus comprises a group of red-colored,Gram-negative,aerobic bacteria that inhabit various marine environments.Several species of Algoriphagus produce the keto-monocyclic carotenoid flexixanthin;however,information on its derivatives and their biological activities is limited.In this study,Algoriphagus sp.strain Fs4 was isolated from the surface of seaweed collected at Nanaehama,Hokkaido,Japan.Based on structural analysis via nuclear magnetic resonance spectroscopy,of the carotenoid produced by the strain,it was identified as 2′-hydroxyflexixanthin,a new carotenoid in the genus Algoriphagus.A comparison of the carotenoid profiles of 25 species of Algoriphagus bacteria revealed that flexixanthin was present in all strains,and some strains also produced 2-or 2′-hydroxyflexixanthin.The biological activities of flexixanthin and its derivatives were evaluated in terms of their antioxidant and anti-inflammatory effects against macrophages.The degree of inhibitory effect on lipid peroxidation was in the order:2-hydroxyflexixanthin>2′-hydroxyflexixanthin>flexixanthin.Conversely,flexixanthin significantly inhibited lipopolysaccharide-induced interleukin-1βand-6,and nitric oxide synthase 2 mRNA expression,demonstrating a stronger inhibitory effect than that of 2′-hydroxyflexixanthin;2-hydroxyflexixanthin showed no significant inhibitory effects.These results indicate that the introduction of hydroxyl groups at specific sites affects the antioxidant and anti-inflammatory activities of flexixanthin.The findings of this study highlights the potential of the genus Algoriphagus as a source of flexix-anthin and its derivatives and provides a basis for the future application of these monocyclic carotenoids in the production of nutraceuticals and pharmaceuticals.
