Konig G

References (5)

Title : Comparative Performance of PETase as a Function of Reaction Conditions, Substrate Properties, and Product Accumulation - Erickson_2022_ChemSusChem_15_e202102517
Author(s) : Erickson E , Shakespeare TJ , Bratti F , Buss BL , Graham R , Hawkins MA , Konig G , Michener WE , Miscall J , Ramirez KJ , Rorrer NA , Zahn M , Pickford AR , McGeehan JE , Beckham GT
Ref : ChemSusChem , 15 :e202102517 , 2022
Abstract : Invited for this month's cover is the BOTTLE Consortium, featuring Gregg Beckham's laboratory from NREL and John McGeehan's laboratory from the University of Portsmouth. The cover image shows the application of poly(ethylene terephthalate) (PET) hydrolase enzymes on post-consumer waste plastic, towards the development of an enzymatic PET recycling strategy. The Full Paper itself is available at 10.1002/cssc.202101932.
ESTHER : Erickson_2022_ChemSusChem_15_e202102517
PubMedSearch : Erickson_2022_ChemSusChem_15_e202102517
PubMedID: 34914860

Title : Sourcing thermotolerant poly(ethylene terephthalate) hydrolase scaffolds from natural diversity - Erickson_2022_Nat.Commun_13_7850
Author(s) : Erickson E , Gado JE , Avilan L , Bratti F , Brizendine RK , Cox PA , Gill R , Graham R , Kim DJ , Konig G , Michener WE , Poudel S , Ramirez KJ , Shakespeare TJ , Zahn M , Boyd ES , Payne CM , Dubois JL , Pickford AR , Beckham GT , McGeehan JE
Ref : Nat Commun , 13 :7850 , 2022
Abstract : Enzymatic deconstruction of poly(ethylene terephthalate) (PET) is under intense investigation, given the ability of hydrolase enzymes to depolymerize PET to its constituent monomers near the polymer glass transition temperature. To date, reported PET hydrolases have been sourced from a relatively narrow sequence space. Here, we identify additional PET-active biocatalysts from natural diversity by using bioinformatics and machine learning to mine 74 putative thermotolerant PET hydrolases. We successfully express, purify, and assay 51 enzymes from seven distinct phylogenetic groups; observing PET hydrolysis activity on amorphous PET film from 37 enzymes in reactions spanning pH from 4.5-9.0 and temperatures from 30-70 degreesC. We conduct PET hydrolysis time-course reactions with the best-performing enzymes, where we observe differences in substrate selectivity as function of PET morphology. We employed X-ray crystallography and AlphaFold to examine the enzyme architectures of all 74 candidates, revealing protein folds and accessory domains not previously associated with PET deconstruction. Overall, this study expands the number and diversity of thermotolerant scaffolds for enzymatic PET deconstruction.
ESTHER : Erickson_2022_Nat.Commun_13_7850
PubMedSearch : Erickson_2022_Nat.Commun_13_7850
PubMedID: 36543766
Gene_locus related to this paper: 9arch-PETcan211 , 9cren-PETcan204 , 9cyan-305pEE028 , 9bact-102Pee006 , 9chlr-7QJM202 , 9bact-a0a656d8b6 , 9actn-a0a1t4kk94 , 9burk-PET11 , 9bact-c3ryl0 , thecs-711Erick , 9actn-RII04304 , 9actn-h6wx58 , thecd-d1a9g5 , thecd-d1a2h1 , 9acto-d4q9n1 , 9acto-f7ix06 , 9gamm-a0a3l8bw54 , 9actn-a0a0n0my27 , 9burk-a0a1e4lw26 , 9actn-Alr407 , 9gamm-a0a3l8bdt3 , 9gamm-a0a2k9lit3 , 9bact-g9by57 , bacsu-pnbae , thefu-q6a0i4 , 9actn-a0a0n0ney5 , 9pseu-a0a1i6nu60 , thefu-q6a0i3 , 9actn-a0a147kjy8 , 9actn-e9upm2

Title : Comparative performance of PETase as a function of reaction conditions, substrate properties, and product accumulation - Erickson_2022_ChemSusChem_15_e202101932
Author(s) : Erickson E , Shakespeare TJ , Bratti F , Buss BL , Graham R , Hawkins MA , Konig G , Michener WE , Miscall J , Ramirez KJ , Rorrer NA , Zahn M , Pickford AR , McGeehan JE , Beckham G
Ref : ChemSusChem , 15 : , 2022
Abstract : There is keen interest to develop new technologies to recycle the plastic poly(ethylene terephthalate) (PET). To this end, the use of PET-hydrolyzing enzymes has shown promise for PET deconstruction to its monomers, terephthalate (TPA) and ethylene glycol (EG). Here, we compare the Ideonella sakaiensis PETase wild-type enzyme to a previously reported improved variant (W159H/S238F). We compare the thermostability of each enzyme and describe a 1.45 A resolution structure of the mutant, highlighting changes in the substrate binding cleft compared to the wild-type enzyme. Subsequently, the performance of the wild-type and variant enzyme was compared as a function of temperature, substrate morphology, and reaction mixture composition. These studies show that reaction temperature has the strongest influence on performance between the two enzymes. We also show that both enzymes achieve higher levels of PET conversion for substrates with moderate crystallinity relative to amorphous substrates. Finally, we assess the impact of product accumulation on reaction progress for the hydrolysis of both PET and bis(2-hydroxyethyl) terephthalate (BHET). Each enzyme displays different inhibition profiles to mono(2-hydroxyethyl) terephthalate (MHET) and TPA, while both are sensitive to inhibition by EG. Overall, this study highlights the importance of reaction conditions, substrate selection, and product accumulation for catalytic performance of PET-hydrolyzing enzymes, which have implications for enzyme screening in the development of enzyme- based polyester recycling.
ESTHER : Erickson_2022_ChemSusChem_15_e202101932
PubMedSearch : Erickson_2022_ChemSusChem_15_e202101932
PubMedID: 34587366
Gene_locus related to this paper: idesa-peth

Title : Poster: The alpha-7 receptor agonist EVP-6124 increases dopamine and glutamate efflux in rat medial prefrontal cortex and nucleus accumbens -
Author(s) : Huang M , Felix AR , Bhuvaneswaran C , Hilt D , Konig G , Meltzer HY
Ref : Biochemical Pharmacology , 82 :1040 , 2011
PubMedID:

Title : Short- and long-term effect of acetylcholinesterase inhibition on the expression and metabolism of the amyloid precursor protein - Racchi_2001_Mol.Psychiatry_6_520
Author(s) : Racchi M , Sironi M , Caprera A , Konig G , Govoni S
Ref : Mol Psychiatry , 6 :520 , 2001
Abstract : We have investigated the acute and chronic effect of metrifonate (MTF) and dichlorvos (DDVP), respectively the prodrug and active acetylcholinesterase inhibitor, on the secretory processing of the amyloid precursor protein (APP) in SH-SY5Y neuroblastoma cells. We demonstrate that the acute treatment of SH-SY5Y cells with both compounds results in an increased secretion of the soluble fragment of APP (sAPPalpha) into the conditioned media of cells, with a pattern correlated to the level of acetycholinesterase inhibition. The regulation of APP processing in these conditions is mediated by an indirect cholinergic effect on muscarinic receptors, as demonstrated by inhibition with atropine. We have also followed APP expression and metabolism after long-term treatment with metrifonate. Treated cells showed reduced AChE activity after 24, 48 h and also following 7 days of repeated treatment, a time point at which increased AChE expression was detectable. At all time points sAPPalpha release was unaffected suggesting that enhanced sAPPalpha release by MTF is transitory, nevertheless the sensitivity of cholinergic receptors was unchanged, as indicated by the fact that cholinergic response can be elicited similarly in untreated and treated cells. APP gene expression was unaffected by long-term AChE inhibition suggesting that increased short-term sAPPalpha release does not elicit compensatory effects.
ESTHER : Racchi_2001_Mol.Psychiatry_6_520
PubMedSearch : Racchi_2001_Mol.Psychiatry_6_520
PubMedID: 11526466