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Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules.

ABSTRACT: Biocatalysis is a key technology enabling plastic recycling. However, despite advances done in the development of plastic-degrading enzymes, the molecular mechanisms that govern their catalytic performance are poorly understood, hampering the engineering of more efficient enzyme-based technologies. In this work, we study the hydrolysis of PET-derived diesters and PET trimers catalyzed by the highly promiscuous lipase B from Candida antarctica (CALB) through QM/MM molecular dynamics simulations supported by experimental Michaelis-Menten kinetics. The computational studies reveal the role of the pH on the CALB regioselectivity toward the hydrolysis of bis-(hydroxyethyl) terephthalate (BHET). We exploit this insight to perform a pH-controlled biotransformation that selectively hydrolyzes BHET to either its corresponding diacid or monoesters using both soluble and immobilized CALB. The discoveries presented here can be exploited for the valorization of BHET resulting from the organocatalytic depolymerization of PET.

SUBMITTER: Swiderek K

PROVIDER: S-EPMC10272158 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules.

Świderek Katarzyna K Velasco-Lozano Susana S Galmés Miquel À MÀ Olazabal Ion I Sardon Haritz H López-Gallego Fernando F Moliner Vicent V

Nature communications 20230615 1

Biocatalysis is a key technology enabling plastic recycling. However, despite advances done in the development of plastic-degrading enzymes, the molecular mechanisms that govern their catalytic performance are poorly understood, hampering the engineering of more efficient enzyme-based technologies. In this work, we study the hydrolysis of PET-derived diesters and PET trimers catalyzed by the highly promiscuous lipase B from Candida antarctica (CALB) through QM/MM molecular dynamics simulations s ...[more]

PMID: 37321996

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Project description:BackgroundPPARs (?,?,?) are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL), an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown.Methods/principal findingsUsing PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL?LDL, IDL) to activate PPAR? preferentially over PPAR? or PPAR?, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPAR? in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPAR? target genes, including adipocyte differentiation related protein (ADRP), angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPAR? activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPAR? activation and ADRP gene regulation in vitro.ConclusionsThese data define a novel pathway involving HL hydrolysis of VLDL that activates PPAR? through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid metabolism that regulate transcription.

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Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules.

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Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules.

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