Inhibition by Carotenoids and Retinoic Acid of Osteoclast-Like Cell Formation Induced by Bone-Resorbing Agents In Vitro.

Ishimi, Yoshiko; Ohmura, Mineko; Wang, Xinxiang; Yamaguchi, Michio; Ikegami, Sachie

doi:10.3164/jcbn.27.113

Cited by 33 publications

(32 citation statements)

References 13 publications

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“…Some are accessory light-harvesting components of photosynthetic systems, while others are photoprotecting antioxidants or regulators of membrane fluidity. Recent studies advocate their effectiveness in preventing cancer and heart disease (36), as well as their potential hormonal activity (5,25). Such diverse molecular functions justify exploring rare or novel carotenoid structures.…”

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confidence: 99%

Evolution of the C ₃₀ Carotenoid Synthase CrtM for Function in a C ₄₀ Pathway

2002

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The C 30 carotene synthase CrtM from Staphylococcus aureus and the C 40 carotene synthase CrtB from Erwinia uredovora were swapped into their respective foreign C 40 and C 30 biosynthetic pathways (heterologously expressed in Escherichia coli) and evaluated for function. Each displayed negligible ability to synthesize the natural carotenoid product of the other. After one round of mutagenesis and screening, we isolated 116 variants of CrtM able to synthesize C 40 carotenoids. In contrast, we failed to find a single variant of CrtB with detectable C 30 activity. Subsequent analysis revealed that the best CrtM mutants performed comparably to CrtB in an in vivo C 40 pathway. These mutants showed significant variation in performance in their original C 30 pathway, indicating the emergence of enzymes with broadened substrate specificity as well as those with shifted specificity. We discovered that Phe 26 alone determines the specificity of CrtM. The plasticity of CrtM with respect to its substrate and product range highlights the potential for creating further new carotenoid backbone structures.

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Evolution of the C ₃₀ Carotenoid Synthase CrtM for Function in a C ₄₀ Pathway

2002

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“…The number of cells stained with the NBT reduction product formazan was decreased by treatment with 10 -5 M lycopene, indicating that lycopene inhibited the formation of ROS-secreting osteoclasts. 110 Ishimi et al 111 (1999) in murine osteoclasts formed in coculture with calvarial osteoblasts. Furthermore, they could not demonstrate any effect of lycopene on bone resorption.…”

Section: Bone Healthmentioning

confidence: 99%

Lycopene: Is it Beneficial to Human Health as an Antioxidant?

Bacanlı¹,

Başaran²,

Başaran³

2017

tjps

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It is well known that free oxygen radicals play an important role in the pathogenesis of several chronic disorders. Antioxidants are known as potential scavengers of reactive oxygen species that can protect biologic membranes against oxidative damage. Recent interest in phytochemicals has increased because of their protective effects against free oxygen radicals. Lycopene, which belongs to the carotenoid family, is the most effective singlet oxygen scavenger in vitro of all the carotenoids. Foods that contain lycopene and related supplements have been reported to prevent chronic diseases including cancer, asthma, and cardiovascular disorders. The aim of the article was to give a brief review of the antioxidant properties and beneficial health effects of lycopene.

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“…We used this information to engineer CrtM variants that can synthesize previously unknown C 45 and C 50 carotenoid backbones (mono-and diisopentenylphytoenes) from the appropriate isoprenyldiphosphate precursors. With this ability to produce new backbones in Escherichia coli comes the potential to generate whole series of novel carotenoids by using carotenoid-modifying enzymes, including desaturases, cyclases, hydroxylases, and dioxygenases, from naturally occurring pathways.Carotenoids are natural pigments with important biological activities (4,10,16,17). Most are based on a 40-carbon (C 40 ) phytoene backbone produced by condensation of 2 molecules of geranylgeranyldiphosphate (GGDP; C 20 PP), a reaction catalyzed by the carotenoid synthase CrtB (Fig.…”

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confidence: 99%

“…Carotenoids are natural pigments with important biological activities (4,10,16,17). Most are based on a 40-carbon (C 40 ) phytoene backbone produced by condensation of 2 molecules of geranylgeranyldiphosphate (GGDP; C 20 PP), a reaction catalyzed by the carotenoid synthase CrtB (Fig.…”

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Evolution of a Pathway to Novel Long-Chain Carotenoids

Umeno

Arnold

2004

J Bacteriol

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Using methods of laboratory evolution to force the C 30 carotenoid synthase CrtM to function as a C 40 synthase, followed by further mutagenesis at functionally important amino acid residues, we have discovered that synthase specificity is controlled at the second (rearrangement) step of the two-step reaction. We used this information to engineer CrtM variants that can synthesize previously unknown C 45 and C 50 carotenoid backbones (mono-and diisopentenylphytoenes) from the appropriate isoprenyldiphosphate precursors. With this ability to produce new backbones in Escherichia coli comes the potential to generate whole series of novel carotenoids by using carotenoid-modifying enzymes, including desaturases, cyclases, hydroxylases, and dioxygenases, from naturally occurring pathways.Carotenoids are natural pigments with important biological activities (4,10,16,17). Most are based on a 40-carbon (C 40 ) phytoene backbone produced by condensation of 2 molecules of geranylgeranyldiphosphate (GGDP; C 20 PP), a reaction catalyzed by the carotenoid synthase CrtB (Fig. 1). The vast majority of the Ͼ700 known carotenoids (9) arise as a result of different types and levels of modification of the C 40 backbone, catalyzed by promiscuous (downstream) carotenoid biosynthetic enzymes (5). A few bacteria, notably Staphylococcus and Heliobacterium spp. (23,24), have a C 30 pathway, which starts with the CrtM synthase-catalyzed condensation of 2 molecules of farnesyldiphosphate (FDP; C 15 PP) to form 4,4Ј-diapophytoene. Yet other bacteria (such as Corynebacterium and Halobacterium spp.) are known to accumulate C 50 carotenoids, but these longer-chain structures are biosynthesized starting from the C 40 structure by the addition of 2 C 5 (isoprene) units (14). Various longer isoprenyldiphosphates are made by different organisms (30) and are potential precursors for longerchain carotenoids. They are precursors to other biosynthetic pathways, however, and no known carotenoids are derived from them. Thus, carotenoid size is tightly controlled by the carotene synthase reaction (20,27).To create new pathways for the biosynthesis of carotenoids with backbones larger than C 40 , we focused on engineering the carotenoid synthase to accept longer diphosphate substrates. Very little is known of the structure or basis for the specificity of these membrane-associated enzymes. Using random mutagenesis and a functional complementation screen for C 40 synthase activity, however, we identified single-amino-acid substitutions in the C 30 synthase CrtM (F26L or F26S) that confer the C 40 function (27). By repeating this experiment with a random mutant library that was free from mutation at F26, we recently found two more amino acid substitutions, W38C and E180G, that confer the same phenotype (26). Upon further mutagenesis at these three residues, we show here that the specificity of the carotenoid synthase CrtM is controlled at the second (rearrangement) step of its two-step reaction. Furthermore, we have engineered synthase variants that can make ...

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Inhibition by Carotenoids and Retinoic Acid of Osteoclast-Like Cell Formation Induced by Bone-Resorbing Agents In Vitro.

Cited by 33 publications

References 13 publications

Evolution of the C ₃₀ Carotenoid Synthase CrtM for Function in a C ₄₀ Pathway

Evolution of the C ₃₀ Carotenoid Synthase CrtM for Function in a C ₄₀ Pathway

Lycopene: Is it Beneficial to Human Health as an Antioxidant?

Evolution of a Pathway to Novel Long-Chain Carotenoids

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Inhibition by Carotenoids and Retinoic Acid of Osteoclast-Like Cell Formation Induced by Bone-Resorbing Agents In Vitro.

Cited by 33 publications

References 13 publications

Evolution of the C 30 Carotenoid Synthase CrtM for Function in a C 40 Pathway

Evolution of the C 30 Carotenoid Synthase CrtM for Function in a C 40 Pathway

Lycopene: Is it Beneficial to Human Health as an Antioxidant?

Evolution of a Pathway to Novel Long-Chain Carotenoids

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Product

Resources

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Evolution of the C ₃₀ Carotenoid Synthase CrtM for Function in a C ₄₀ Pathway

Evolution of the C ₃₀ Carotenoid Synthase CrtM for Function in a C ₄₀ Pathway