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  1. Article: Targeting hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase for lignin modification in Brachypodium distachyon.

    Serrani-Yarce, Juan Carlos / Escamilla-Trevino, Luis / Barros, Jaime / Gallego-Giraldo, Lina / Pu, Yunqiao / Ragauskas, Art / Dixon, Richard A

    Biotechnology for biofuels

    2021  Volume 14, Issue 1, Page(s) 50

    Abstract: Background: Hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) is a central enzyme ...

    Abstract Background: Hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) is a central enzyme of the so-called "esters" pathway to monolignols. As originally envisioned, HCT functions twice in this pathway, to form coumaroyl shikimate and then, in the "reverse" direction, to convert caffeoyl shikimate to caffeoyl CoA. The discovery of a caffeoyl shikimate esterase (CSE) that forms caffeic acid directly from caffeoyl shikimate calls into question the need for the reverse HCT reaction in lignin biosynthesis. Loss of function of HCT gives severe growth phenotypes in several dicot plants, but less so in some monocots, questioning whether this enzyme, and therefore the shikimate shunt, plays the same role in both monocots and dicots. The model grass Brachypodium distachyon has two HCT genes, but lacks a classical CSE gene. This study was therefore conducted to evaluate the utility of HCT as a target for lignin modification in a species with an "incomplete" shikimate shunt.
    Results: The kinetic properties of recombinant B. distachyon HCTs were compared with those from Arabidopsis thaliana, Medicago truncatula, and Panicum virgatum (switchgrass) for both the forward and reverse reactions. Along with two M. truncatula HCTs, B. distachyon HCT2 had the least kinetically unfavorable reverse HCT reaction, and this enzyme is induced when HCT1 is down-regulated. Down regulation of B. distachyon HCT1, or co-down-regulation of HCT1 and HCT2, by RNA interference led to reduced lignin levels, with only modest changes in lignin composition and molecular weight.
    Conclusions: Down-regulation of HCT1, or co-down-regulation of both HCT genes, in B. distachyon results in less extensive changes in lignin content/composition and cell wall structure than observed following HCT down-regulation in dicots, with little negative impact on biomass yield. Nevertheless, HCT down-regulation leads to significant improvements in biomass saccharification efficiency, making this gene a preferred target for biotechnological improvement of grasses for bioprocessing.
    Language English
    Publishing date 2021-02-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2421351-2
    ISSN 1754-6834
    ISSN 1754-6834
    DOI 10.1186/s13068-021-01905-1
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  2. Article: Targeting hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase for lignin modification in Brachypodium distachyon

    Serrani-Yarce, Juan Carlos / Escamilla-Trevino, Luis / Barros, Jaime / Gallego-Giraldo, Lina / Pu, Yunqiao / Ragauskas, Art / Dixon, Richard A.

    Biotechnology for biofuels. 2021 Dec., v. 14, no. 1

    2021  

    Abstract: BACKGROUND: Hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) is a central enzyme ...

    Abstract BACKGROUND: Hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) is a central enzyme of the so-called “esters” pathway to monolignols. As originally envisioned, HCT functions twice in this pathway, to form coumaroyl shikimate and then, in the “reverse” direction, to convert caffeoyl shikimate to caffeoyl CoA. The discovery of a caffeoyl shikimate esterase (CSE) that forms caffeic acid directly from caffeoyl shikimate calls into question the need for the reverse HCT reaction in lignin biosynthesis. Loss of function of HCT gives severe growth phenotypes in several dicot plants, but less so in some monocots, questioning whether this enzyme, and therefore the shikimate shunt, plays the same role in both monocots and dicots. The model grass Brachypodium distachyon has two HCT genes, but lacks a classical CSE gene. This study was therefore conducted to evaluate the utility of HCT as a target for lignin modification in a species with an “incomplete” shikimate shunt. RESULTS: The kinetic properties of recombinant B. distachyon HCTs were compared with those from Arabidopsis thaliana, Medicago truncatula, and Panicum virgatum (switchgrass) for both the forward and reverse reactions. Along with two M. truncatula HCTs, B. distachyon HCT2 had the least kinetically unfavorable reverse HCT reaction, and this enzyme is induced when HCT1 is down-regulated. Down regulation of B. distachyon HCT1, or co-down-regulation of HCT1 and HCT2, by RNA interference led to reduced lignin levels, with only modest changes in lignin composition and molecular weight. CONCLUSIONS: Down-regulation of HCT1, or co-down-regulation of both HCT genes, in B. distachyon results in less extensive changes in lignin content/composition and cell wall structure than observed following HCT down-regulation in dicots, with little negative impact on biomass yield. Nevertheless, HCT down-regulation leads to significant improvements in biomass saccharification efficiency, making this gene a preferred target for biotechnological improvement of grasses for bioprocessing.
    Keywords Arabidopsis thaliana ; Brachypodium distachyon ; Medicago truncatula ; Panicum virgatum ; RNA interference ; biofuels ; biomass production ; bioprocessing ; biosynthesis ; biotechnology ; caffeic acid ; cell walls ; esterases ; genes ; grasses ; hydroxycinnamoyltransferase ; lignin ; lignin content ; molecular weight ; saccharification
    Language English
    Dates of publication 2021-12
    Size p. 50.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2421351-2
    ISSN 1754-6834
    ISSN 1754-6834
    DOI 10.1186/s13068-021-01905-1
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  3. Article ; Online: Structural studies of cinnamoyl-CoA reductase and cinnamyl-alcohol dehydrogenase, key enzymes of monolignol biosynthesis.

    Pan, Haiyun / Zhou, Rui / Louie, Gordon V / Mühlemann, Joëlle K / Bomati, Erin K / Bowman, Marianne E / Dudareva, Natalia / Dixon, Richard A / Noel, Joseph P / Wang, Xiaoqiang

    The Plant cell

    2014  Volume 26, Issue 9, Page(s) 3709–3727

    Abstract: The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two ... key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks ...

    Abstract The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks for lignin polymers in plant cell walls. Here, we describe detailed functional and structural analyses of CCRs from Medicago truncatula and Petunia hybrida and of an atypical CAD (CAD2) from M. truncatula. These enzymes are closely related members of the short-chain dehydrogenase/reductase (SDR) superfamily. Our structural studies support a reaction mechanism involving a canonical SDR catalytic triad in both CCR and CAD2 and an important role for an auxiliary cysteine unique to CCR. Site-directed mutants of CAD2 (Phe226Ala and Tyr136Phe) that enlarge the phenolic binding site result in a 4- to 10-fold increase in activity with sinapaldehyde, which in comparison to the smaller coumaraldehyde and coniferaldehyde substrates is disfavored by wild-type CAD2. This finding demonstrates the potential exploitation of rationally engineered forms of CCR and CAD2 for the targeted modification of monolignol composition in transgenic plants. Thermal denaturation measurements and structural comparisons of various liganded and unliganded forms of CCR and CAD2 highlight substantial conformational flexibility of these SDR enzymes, which plays an important role in the establishment of catalytically productive complexes of the enzymes with their NADPH and phenolic substrates.
    MeSH term(s) Alcohol Oxidoreductases/chemistry ; Alcohol Oxidoreductases/metabolism ; Aldehyde Oxidoreductases/chemistry ; Aldehyde Oxidoreductases/metabolism ; Binding Sites ; Biocatalysis ; Cloning, Molecular ; Crystallography, X-Ray ; Cysteine/metabolism ; Disulfides/metabolism ; Esters/metabolism ; Kinetics ; Ligands ; Lignin/biosynthesis ; Lignin/chemistry ; Medicago truncatula/enzymology ; Models, Molecular ; Mutant Proteins/chemistry ; Mutant Proteins/metabolism ; NADP/metabolism ; Petunia/enzymology ; Propanols/chemistry ; Propanols/metabolism ; Structural Homology, Protein ; Substrate Specificity ; Temperature
    Chemical Substances Disulfides ; Esters ; Ligands ; Mutant Proteins ; Propanols ; NADP (53-59-8) ; Lignin (9005-53-2) ; Alcohol Oxidoreductases (EC 1.1.-) ; cinnamyl alcohol dehydrogenase (EC 1.1.1.195) ; Aldehyde Oxidoreductases (EC 1.2.-) ; cinnamoyl CoA reductase (EC 1.2.1.44) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2014-09-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 623171-8
    ISSN 1532-298X ; 1040-4651
    ISSN (online) 1532-298X
    ISSN 1040-4651
    DOI 10.1105/tpc.114.127399
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Expanding the Concept of Caregiver Supervision to Prevent Child Drowning.

    Schwebel, David C / Ramos, William / Gilchrist, Julie / Dixon, Cinnamon A

    Pediatrics

    2023  Volume 151, Issue 3

    MeSH term(s) Humans ; Child ; Infant ; Drowning/prevention & control ; Caregivers ; Parents ; Surveys and Questionnaires
    Language English
    Publishing date 2023-02-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207677-9
    ISSN 1098-4275 ; 0031-4005
    ISSN (online) 1098-4275
    ISSN 0031-4005
    DOI 10.1542/peds.2022-060240
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  5. Article ; Online: Into the Future of Pediatric Trauma and Critical Care Science.

    Dixon, Cinnamon A / Jenkins, Tammara / Maholmes, Valerie

    JAMA pediatrics

    2022  Volume 177, Issue 1, Page(s) 5–6

    MeSH term(s) Child ; Humans ; United States ; Critical Care ; National Institute of Child Health and Human Development (U.S.)
    Language English
    Publishing date 2022-11-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2701223-2
    ISSN 2168-6211 ; 2168-6203
    ISSN (online) 2168-6211
    ISSN 2168-6203
    DOI 10.1001/jamapediatrics.2022.4577
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  6. Article ; Online: Paws to Care: Implementation of a Novel Medical Dog Office Hours Program to Foster Pediatric Health Care Staff Resilience and Joy.

    Gerson, Jennifer S / Marco, Kizzy C / Staab, Jennifer H / Dixon, Cinnamon A

    Clinical pediatrics

    2023  Volume 62, Issue 8, Page(s) 849–855

    Abstract: Burnout and resiliency are significant challenges among health care workers. Animal-assisted therapy (AAT) has shown to improve patient-level outcomes; however, AAT research involving hospital staff is limited. Our novel Medical Dog ("MD") Office Hours ... ...

    Abstract Burnout and resiliency are significant challenges among health care workers. Animal-assisted therapy (AAT) has shown to improve patient-level outcomes; however, AAT research involving hospital staff is limited. Our novel Medical Dog ("MD") Office Hours Program aimed to provide support to pediatric hospital staff and explore the program's impact on burnout. Participant surveys described work role and years of experience, well-being, and emotional/physical descriptions and symptoms. Of 149 participants, 85% endorsed baseline distress/burnout; nearly half had at-risk Well-Being Index scores. Compared with baseline, postintervention participants endorsed significantly fewer negative (more positive) emotions; greater feelings of comfort and energy; and decreased tiredness and pain (
    MeSH term(s) Humans ; Dogs ; Animals ; Animal Assisted Therapy ; Resilience, Psychological ; Burnout, Professional/prevention & control ; Burnout, Professional/psychology ; Personnel, Hospital ; Surveys and Questionnaires ; Delivery of Health Care
    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 207678-0
    ISSN 1938-2707 ; 0009-9228
    ISSN (online) 1938-2707
    ISSN 0009-9228
    DOI 10.1177/00099228231152860
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  7. Article ; Online: Sustainable biosynthetic pathways to value-added bioproducts from hydroxycinnamic acids.

    Tramontina, Robson / Ciancaglini, Iara / Roman, Ellen K B / Chacón, Micaela G / Corrêa, Thamy L R / Dixon, Neil / Bugg, Timothy D H / Squina, Fabio Marcio

    Applied microbiology and biotechnology

    2023  Volume 107, Issue 13, Page(s) 4165–4185

    Abstract: ... The hydroxycinnamic acid fraction of lignocellulosic biomass represents an untapped source of aromatic molecules ... in the development of a biorefinery concept based on the biocatalytic conversion of the hydroxycinnamic acids ferulic ... pathways in the context of biorefineries • Description of pathways from hydroxycinnamic acids to high-value ...

    Abstract The biorefinery concept, in which biomass is utilized for the production of fuels and chemicals, emerges as an eco-friendly, cost-effective, and renewable alternative to petrochemical-based production. The hydroxycinnamic acid fraction of lignocellulosic biomass represents an untapped source of aromatic molecules that can be converted to numerous high-value products with industrial applications, including in the flavor and fragrance sector and pharmaceuticals. This review describes several biochemical pathways useful in the development of a biorefinery concept based on the biocatalytic conversion of the hydroxycinnamic acids ferulic, caffeic, and p-coumaric acid into high-value molecules. KEY POINTS: • The phenylpropanoids bioconversion pathways in the context of biorefineries • Description of pathways from hydroxycinnamic acids to high-value compounds • Metabolic engineering and synthetic biology advance hydroxycinnamic acid-based biorefineries.
    MeSH term(s) Coumaric Acids/metabolism ; Biosynthetic Pathways ; Biomass ; Biocatalysis ; Metabolic Engineering
    Chemical Substances Coumaric Acids
    Language English
    Publishing date 2023-05-22
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 392453-1
    ISSN 1432-0614 ; 0171-1741 ; 0175-7598
    ISSN (online) 1432-0614
    ISSN 0171-1741 ; 0175-7598
    DOI 10.1007/s00253-023-12571-8
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  8. Article ; Online: Dog Bites in Children Surge during Coronavirus Disease-2019: A Case for Enhanced Prevention.

    Dixon, Cinnamon A / Mistry, Rakesh D

    The Journal of pediatrics

    2020  Volume 225, Page(s) 231–232

    MeSH term(s) Animals ; Betacoronavirus ; Bites and Stings/epidemiology ; Bites and Stings/prevention & control ; COVID-19 ; Child ; Coronavirus Infections/epidemiology ; Dogs ; Emergency Service, Hospital/statistics & numerical data ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology ; SARS-CoV-2 ; Stress, Psychological
    Keywords covid19
    Language English
    Publishing date 2020-06-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3102-1
    ISSN 1097-6833 ; 0022-3476
    ISSN (online) 1097-6833
    ISSN 0022-3476
    DOI 10.1016/j.jpeds.2020.06.071
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  9. Article: Structural Studies of Cinnamoyl-CoA Reductase and Cinnamyl-Alcohol Dehydrogenase, Key Enzymes of Monolignol Biosynthesis

    Pan, Haiyun / Erin K. Bomati / Gordon V. Louie / Joëlle K. Mëühlemann / Joseph P. Noel / Marianne E. Bowman / Natalia Dudareva / Richard A. Dixon / Rui Zhou / Xiaoqiang Wang

    plant cell. 2014 Sept., v. 26, no. 9

    2014  

    Abstract: The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two ... and phenolicinnamoyl-CoA reductase (CCR) and cin substrates. ... key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks ...

    Abstract The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks for lignin polymers in plant cell walls. Here, we describe detailed functional and structural analyses of CCRs from Medicago truncatula and Petunia hybrida and of an atypical CAD (CAD2) from M. truncatula . These enzymes are closely related members of the short-chain dehydrogenase/reductase (SDR) superfamily. Our structural studies support a reaction mechanism involving a canonical SDR catalytic triad in both CCR and CAD2 and an important role for an auxiliary cysteine unique to CCR. Site-directed mutants of CAD2 (Phe226Ala and Tyr136Phe) that enlarge the phenolic binding site result in a 4- to 10-fold increase in activity with sinapaldehyde, which in comparison to the smaller coumaraldehyde and coniferaldehyde substrates is disfavored by wild-type CAD2. This finding demonstrates the potential exploitation of rationally engineered forms of CCR and CAD2 for the targeted modification of monolignol composition in transgenic plants. Thermal denaturation measurements and structural comparisons of various liganded and unliganded forms of CCR and CAD2 highlight substantial conformational flexibility of these SDR enzymes, which plays an important role in the establishment of catalytically productive complexes of the enzymes with their NADPH and phenolic substrates.

    The enzymes cinnamoyl-CoA reductase and cinnamyl-alcohol dehydrogenase participate in the generation of building blocks for plant lignin-polymers. Their structures reported here shed light on the mechanisms of enzyme activity and regulation and on the determinants of substrate specificity. These findings may ultimately aid in the rational engineering of lignin composition in plants.
    Keywords biosynthesis ; cinnamoyl-CoA reductase ; engineering ; enzyme activity ; lignin ; substrate specificity
    Language English
    Dates of publication 2014-09
    Size p. 3709-3727.
    Publishing place American Society of Plant Biologists
    Document type Article
    ZDB-ID 623171-8
    ISSN 1532-298X ; 1040-4651
    ISSN (online) 1532-298X
    ISSN 1040-4651
    DOI 10.1105/tpc.114.127399
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  10. Article ; Online: Distinct cinnamoyl CoA reductases involved in parallel routes to lignin in Medicago truncatula.

    Zhou, Rui / Jackson, Lisa / Shadle, Gail / Nakashima, Jin / Temple, Stephen / Chen, Fang / Dixon, Richard A

    Proceedings of the National Academy of Sciences of the United States of America

    2010  Volume 107, Issue 41, Page(s) 17803–17808

    Abstract: Cinnamoyl CoA reductases (CCR) convert hydroxycinnamoyl CoA esters to their corresponding cinnamyl ...

    Abstract Cinnamoyl CoA reductases (CCR) convert hydroxycinnamoyl CoA esters to their corresponding cinnamyl aldehydes in monolignol biosynthesis. We identified two CCR genes in the model legume Medicago truncatula. CCR1 exhibits preference for feruloyl CoA, but CCR2 prefers caffeoyl and 4-coumaroyl CoAs, exhibits sigmoidal kinetics with these substrates, and is substrate-inhibited by feruloyl and sinapoyl CoAs. M. truncatula lines harboring transposon insertions in CCR1 exhibit drastically reduced growth and lignin content, whereas CCR2 knockouts grow normally with moderate reduction in lignin levels. CCR1 fully and CCR2 partially complement the irregular xylem gene 4 CCR mutation of Arabidopsis. The expression of caffeoyl CoA 3-O-methyltransferase (CCoAOMT) is up-regulated in CCR2 knockout lines; conversely, knockout of CCoAOMT up-regulates CCR2. These observations suggest that CCR2 is involved in a route to monolignols in Medicago whereby coniferaldehyde is formed via caffeyl aldehyde which then is 3-O-methylated by caffeic acid O-methyltransferase.
    MeSH term(s) Aldehyde Oxidoreductases/metabolism ; Arabidopsis ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; In Situ Hybridization ; Kinetics ; Lignin/biosynthesis ; Medicago truncatula/enzymology ; Medicago truncatula/genetics ; Methyltransferases/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Substrate Specificity
    Chemical Substances Lignin (9005-53-2) ; Aldehyde Oxidoreductases (EC 1.2.-) ; cinnamoyl CoA reductase (EC 1.2.1.44) ; Methyltransferases (EC 2.1.1.-) ; caffeoyl-CoA O-methyltransferase (EC 2.1.1.104)
    Language English
    Publishing date 2010-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1012900107
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