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Author Report for: Schumacher J

Title: An archaeal lid-containing feruloyl esterase degrades polyethylene terephthalate
Perez-Garcia P, Chow J, Costanzi E, Gurschke M, Dittrich J, Dierkes RF, Molitor R, Applegate V, Feuerriegel G and Streit WR <9 more author(s)> Perez-Garcia P, Chow J, Costanzi E, Gurschke M, Dittrich J, Dierkes RF, Molitor R, Applegate V, Feuerriegel G, Tete P, Danso D, Thies S, Schumacher J, Pfleger C, Jaeger KE, Gohlke H, Smits SHJ, Schmitz RA, Streit WR (- 9)
Ref: Commun Chem, 6:193, 2023 : PubMed
Abstract


ESTHER: Perez-Garcia_2023_Commun.Chem_6_193
PubMedSearch: Perez-Garcia 2023 Commun.Chem 6 193
PubMedID: 37697032
Gene_locus related to this paper: 9arch-PET46

Abstract

Polyethylene terephthalate (PET) is a commodity polymer known to globally contaminate marine and terrestrial environments. Today, around 80 bacterial and fungal PET-active enzymes (PETases) are known, originating from four bacterial and two fungal phyla. In contrast, no archaeal enzyme had been identified to degrade PET. Here we report on the structural and biochemical characterization of PET46 (RLI42440.1), an archaeal promiscuous feruloyl esterase exhibiting degradation activity on semi-crystalline PET powder comparable to IsPETase and LCC (wildtypes), and higher activity on bis-, and mono-(2-hydroxyethyl) terephthalate (BHET and MHET). The enzyme, found by a sequence-based metagenome search, is derived from a non-cultivated, deep-sea Candidatus Bathyarchaeota archaeon. Biochemical characterization demonstrated that PET46 is a promiscuous, heat-adapted hydrolase. Its crystal structure was solved at a resolution of 1.71A. It shares the core alpha/beta-hydrolase fold with bacterial PETases, but contains a unique lid common in feruloyl esterases, which is involved in substrate binding. Thus, our study widens the currently known diversity of PET-hydrolyzing enzymes, by demonstrating PET depolymerization by a plant cell wall-degrading esterase.



        

Title: Structural and molecular cholinergic imaging markers of cognitive decline in Parkinson's disease
Schumacher J, Kanel P, Dyrba M, Storch A, Bohnen NI, Teipel S, Grothe MJ
Ref: Brain, :, 2023 : PubMed
Abstract


ESTHER: Schumacher_2023_Brain__
PubMedSearch: Schumacher 2023 Brain
PubMedID: 37403733

Abstract

Cognitive decline in Parkinson's disease is related to cholinergic system degeneration which can be assessed in vivo using structural MRI markers of basal forebrain volume and PET measures of cortical cholinergic activity. In the present study we aimed to examine the interrelation between basal forebrain degeneration and PET-measured depletion of cortical acetylcholinesterase activity as well as their relative contribution to cognitive impairment in Parkinson's disease. This cross-sectional study included 143 Parkinson's disease participants without dementia and 52 healthy control participants who underwent structural MRI, PET scanning with [11C]-methyl-4-piperidinyl propionate (PMP) as a measure of cortical acetylcholinesterase activity, and a detailed cognitive assessment. Based on the 5th percentile of the overall cortical PMP PET signal from the control group, people with Parkinson's disease were subdivided into a normo-cholinergic (N=94) and a hypo-cholinergic group (N=49). Volumes of functionally defined posterior and anterior basal forebrain sub-regions were extracted using an established automated MRI volumetry approach based on a stereotactic atlas of cholinergic basal forebrain nuclei. We used Bayesian t-tests to compare basal forebrain volumes between controls, and normo- and hypo-cholinergic Parkinson's participants after covarying out age, sex, and years of education. Associations between the two cholinergic imaging measures were assessed across all people with Parkinson's using Bayesian correlations and their respective relations with performance in different cognitive domains were assessed with Bayesian ANCOVAs. As a specificity analysis, hippocampal volume was added to the analysis. We found evidence for a reduction of posterior basal forebrain volume in the hypo-cholinergic compared to both normo-cholinergic Parkinson's (Bayes Factor against the null model (BF10)=8.2) and control participants (BF10=6.0), while for the anterior basal forebrain the evidence was inconclusive (BF10<3). In continuous association analyses, posterior basal forebrain volume was significantly associated with cortical PMP PET signal in a temporo-posterior distribution. The combined models for the prediction of cognitive scores showed that both cholinergic markers (posterior basal forebrain volume and cortical PMP PET signal) were independently related to multi-domain cognitive deficits, and were more important predictors for all cognitive scores, including memory scores, than hippocampal volume. We conclude that degeneration of the posterior basal forebrain in Parkinson's disease is accompanied by functional cortical changes in acetylcholinesterase activity and that both PET and MRI cholinergic imaging markers are independently associated with multi-domain cognitive deficits in Parkinson's disease without dementia. Comparatively, hippocampal atrophy only seems to have minimal involvement in the development of early cognitive impairment in Parkinson's disease.



        

Title: An archaeal lid-containing feruloyl-esterase degrades polyethylene terephthalate (PET)
Perez-Garcia P, Chow J, Costanzi E, Gurschke M, Dittrich J, Dierkes RF, Molitor R, Applegate V, Feuerriegel G and Streit WR <9 more author(s)> Perez-Garcia P, Chow J, Costanzi E, Gurschke M, Dittrich J, Dierkes RF, Molitor R, Applegate V, Feuerriegel G, Tete P, Danso D, Thies S, Schumacher J, Pfleger C, Jaeger KE, Gohlke H, Smits SHJ, Schmitz RA, Streit WR (- 9)
Ref: ResearchSquare, :, 2023 : PubMed
Abstract


ESTHER: Streit_2023_ResearchSquare__
PubMedSearch: Streit 2023 ResearchSquare
Gene_locus related to this paper: 9arch-PETcan211, 9cren-PETcan204, 9arch-PET46

Abstract

https://www.researchsquare.com/article/rs-3196380/latest.pdf Polyethylene terephthalate (PET) is a commodity polymer known to globally contaminate marine and terrestrial environments. Today, around 80 bacterial and fungal PET-active enzymes (PETases) are known, originating from four bacterial and two fungal phyla. In contrast, no archaeal enzyme has been identified to degrade PET. Here we report on the structural and biochemical characterization of PET46, an archaeal promiscuous feruloyl esterase exhibiting degradation activity on semi-crystalline PET powder comparable to IsPETase and LCC (wildtypes), and higher activity on bis-, and mono-(2-hydroxyethyl) terephthalate (BHET and MHET). The enzyme, found by a sequence-based metagenome search, was derived from a non-cultivated, deep-sea Candidatus Bathyarchaeota archaeon. Biochemical characterization demonstrated that PET46 is a promiscuous, heat-adapted hydrolase. Its crystal structure was solved at a resolution of 1.71 A. It shares the core alpha/beta-hydrolase fold with bacterial PETases, but contains a unique lid common in feruloyl esterases, which is involved in substrate binding. Thus, our study widens the currently known diversity of PET-hydrolyzing enzymes, by demonstrating PET depolymerization by a plant cell wall-degrading esterase.



        

Title: The Bacteroidetes Aequorivita sp. and Kaistella jeonii Produce Promiscuous Esterases With PET-Hydrolyzing Activity
Zhang H, Perez-Garcia P, Dierkes RF, Applegate V, Schumacher J, Chibani CM, Sternagel S, Preuss L, Weigert S and Streit WR <9 more author(s)> Zhang H, Perez-Garcia P, Dierkes RF, Applegate V, Schumacher J, Chibani CM, Sternagel S, Preuss L, Weigert S, Schmeisser C, Danso D, Pleiss J, Almeida A, Hocker B, Hallam SJ, Schmitz RA, Smits SHJ, Chow J, Streit WR (- 9)
Ref: Front Microbiol, 12:803896, 2021 : PubMed
Abstract


ESTHER: Zhang_2022_Front.Microbiol_12_803896
PubMedSearch: Zhang 2022 Front.Microbiol 12 803896
PubMedID: 35069509
Gene_locus related to this paper: flutr-f2ie04, 9flao-a0a0c1f4u8, 9flao-kjj39608, 9flao-a0a330mq60

Abstract

Certain members of the Actinobacteria and Proteobacteria are known to degrade polyethylene terephthalate (PET). Here, we describe the first functional PET-active enzymes from the Bacteroidetes phylum. Using a PETase-specific Hidden-Markov-Model- (HMM-) based search algorithm, we identified several PETase candidates from Flavobacteriaceae and Porphyromonadaceae. Among them, two promiscuous and cold-active esterases derived from Aequorivita sp. (PET27) and Kaistella jeonii (PET30) showed depolymerizing activity on polycaprolactone (PCL), amorphous PET foil and on the polyester polyurethane Impranil((a)) DLN. PET27 is a 37.8 kDa enzyme that released an average of 174.4 nmol terephthalic acid (TPA) after 120 h at 30 degreesC from a 7 mg PET foil platelet in a 200 microl reaction volume, 38-times more than PET30 (37.4 kDa) released under the same conditions. The crystal structure of PET30 without its C-terminal Por-domain (PET30deltaPorC) was solved at 2.1 A and displays high structural similarity to the IsPETase. PET30 shows a Phe-Met-Tyr substrate binding motif, which seems to be a unique feature, as IsPETase, LCC and PET2 all contain Tyr-Met-Trp binding residues, while PET27 possesses a Phe-Met-Trp motif that is identical to Cut190. Microscopic analyses showed that K. jeonii cells are indeed able to bind on and colonize PET surfaces after a few days of incubation. Homologs of PET27 and PET30 were detected in metagenomes, predominantly aquatic habitats, encompassing a wide range of different global climate zones and suggesting a hitherto unknown influence of this bacterial phylum on man-made polymer degradation.



        

Title: In vivo nucleus basalis of Meynert degeneration in mild cognitive impairment with Lewy bodies
Schumacher J, Taylor JP, Hamilton CA, Firbank M, Cromarty RA, Donaghy PC, Roberts G, Allan L, Lloyd J and Thomas AJ <3 more author(s)> Schumacher J, Taylor JP, Hamilton CA, Firbank M, Cromarty RA, Donaghy PC, Roberts G, Allan L, Lloyd J, Durcan R, Barnett N, O'Brien JT, Thomas AJ (- 3)
Ref: Neuroimage Clin, 30:102604, 2021 : PubMed
Abstract


ESTHER: Schumacher_2021_Neuroimage.Clin_30_102604
PubMedSearch: Schumacher 2021 Neuroimage.Clin 30 102604
PubMedID: 33711623

Abstract

OBJECTIVES: To investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. METHODS: We studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer's disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. RESULTS: Overall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. CONCLUSIONS: This study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group.



        

Title: Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea
Amselem J, Cuomo CA, van Kan JA, Viaud M, Benito EP, Couloux A, Coutinho PM, de Vries RP, Dyer PS and Dickman M <62 more author(s)> Amselem J, Cuomo CA, van Kan JA, Viaud M, Benito EP, Couloux A, Coutinho PM, de Vries RP, Dyer PS, Fillinger S, Fournier E, Gout L, Hahn M, Kohn L, Lapalu N, Plummer KM, Pradier JM, Quevillon E, Sharon A, Simon A, ten Have A, Tudzynski B, Tudzynski P, Wincker P, Andrew M, Anthouard V, Beever RE, Beffa R, Benoit I, Bouzid O, Brault B, Chen Z, Choquer M, Collemare J, Cotton P, Danchin EG, Da Silva C, Gautier A, Giraud C, Giraud T, Gonzalez C, Grossetete S, Guldener U, Henrissat B, Howlett BJ, Kodira C, Kretschmer M, Lappartient A, Leroch M, Levis C, Mauceli E, Neuveglise C, Oeser B, Pearson M, Poulain J, Poussereau N, Quesneville H, Rascle C, Schumacher J, Segurens B, Sexton A, Silva E, Sirven C, Soanes DM, Talbot NJ, Templeton M, Yandava C, Yarden O, Zeng Q, Rollins JA, Lebrun MH, Dickman M (- 62)
Ref: PLoS Genet, 7:e1002230, 2011 : PubMed
Abstract


ESTHER: Amselem_2011_PLoS.Genet_7_E1002230
PubMedSearch: Amselem 2011 PLoS.Genet 7 E1002230
PubMedID: 21876677
Gene_locus related to this paper: botci-cutas, botci-q6rki2, botf4-g2y7k8, botfb-dapb, botfu-g2xyd8, botfu-g2ynh8, scls1-a7e814, scls1-a7edc9, scls1-a7edh1, scls1-a7emm0, scls1-a7eti8, scls1-a7eu48, scls1-a7f208, scls1-dapb, botf4-g2xqp7, scls1-a7eqq8, botf4-g2xqc6, scls1-a7ebs4, botf4-g2xn51, scls1-a7f5m9, botf4-g2xti4, botf4-g2xtu7, botf4-g2yfp1, scls1-a7f534, botf4-g2yys3, scls1-a7erz9, botf4-g2y037, botf4-g2y0e1, scls1-a7f706, scls1-a7ewt6, botf4-g2yuj6, botf1-m7u3d1, botf1-m7u430, botf1-m7tei8, botf1-m7u0w9, botf1-m7tij6, botf1-m7u819, botf1-m7u6d8, botf1-m7tzd4, botf1-m7tqd7, botf1-m7tyz9, botf1-m7unl9, botf1-m7u429, botf1-m7u4s5, botf1-m7ul92, botf1-m7tx42, botf1-m7u9h4, botf1-m7u187, botf1-m7uz64, botf1-m7u4q4, botf1-m7u2f6, botf1-m7tt59, botf1-m7v3h2, botf1-m7u6c9, botf1-m7tud9, botf1-m7u309, scls1-a7et87, botf4-g2ylt4, scls1-a7f5a0, scls1-a7f900, botf4-g2yib9, scls1-a7f3m9, scls1-a7er46, botf4-g2y3y4, botf4-g2xyy5, botf1-m7uct5, scls1-a7ea78, scls1-kex1, scls1-cbpya, botfb-cbpya

Abstract

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38-39 Mb genomes include 11,860-14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea-specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops.



        

Title: The Botrytis cinerea phytotoxin botcinic acid requires two polyketide synthases for production and has a redundant role in virulence with botrydial
Dalmais B, Schumacher J, Moraga J, P LEP, Tudzynski B, Collado IG, Viaud M
Ref: Mol Plant Pathol, 12:564, 2011 : PubMed
Abstract


ESTHER: Dalmais_2011_Mol.Plant.Pathol_12_564
PubMedSearch: Dalmais 2011 Mol.Plant.Pathol 12 564
PubMedID: 21722295
Gene_locus related to this paper: botfb-boa10

Abstract

The grey mould fungus Botrytis cinerea produces two major phytotoxins, the sesquiterpene botrydial, for which the biosynthesis gene cluster has been characterized previously, and the polyketide botcinic acid. We have identified two polyketide synthase (PKS) encoding genes, BcPKS6 and BcPKS9, that are up-regulated during tomato leaf infection. Gene inactivation and analysis of the secondary metabolite spectra of several independent mutants demonstrated that both BcPKS6 and BcPKS9 are key enzymes for botcinic acid biosynthesis. We showed that BcPKS6 and BcPKS9 genes, renamed BcBOA6 and BcBO9 (for B. cinerea botcinic acid biosynthesis), are located at different genomic loci, each being adjacent to other putative botcinic acid biosynthetic genes, named BcBOA1 to BcBOA17. Putative orthologues of BcBOA genes are present in the closely related fungus Sclerotinia sclerotiorum, but the cluster organization is not conserved between the two species. As for the botrydial biosynthesis genes, the expression of BcBOA genes is co-regulated by the Galpha subunit BCG1 during both in vitro and in planta growth. The loss of botcinic acid production does not affect virulence on bean and tomato leaves. However, double mutants that do not produce botcinic acid or botrydial (bcpks6deltabcbot2delta) exhibit markedly reduced virulence. Hence, a redundant role of botrydial and botcinic acid in the virulence of B. cinerea has been demonstrated.