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International Journal of Molecular... Sep 2022Processes involving lipases in obtaining active pharmaceutical ingredients (APIs) are crucial to increase the sustainability of the industry. Despite their lower... (Review)
Review
Processes involving lipases in obtaining active pharmaceutical ingredients (APIs) are crucial to increase the sustainability of the industry. Despite their lower production cost, microbial lipases are striking for their versatile catalyzing reactions beyond their physiological role. In the context of taking advantage of microbial lipases in reactions for the synthesis of API building blocks, this review focuses on: (i) the structural origins of the catalytic properties of microbial lipases, including the results of techniques such as single particle monitoring (SPT) and the description of its selectivity beyond the Kazlauskas rule as the "Mirror-Image Packing" or the "Key Region(s) rule influencing enantioselectivity" (KRIE); (ii) immobilization methods given the conferred operative advantages in industrial applications and their modulating capacity of lipase properties; and (iii) a comprehensive description of microbial lipases use as a conventional or promiscuous catalyst in key reactions in the organic synthesis (Knoevenagel condensation, Morita-Baylis-Hillman (MBH) reactions, Markovnikov additions, Baeyer-Villiger oxidation, racemization, among others). Finally, this review will also focus on a research perspective necessary to increase microbial lipases application development towards a greener industry.
Topics: Catalysis; Chemistry Techniques, Synthetic; Industry; Lipase; Pharmaceutical Preparations
PubMed: 36077332
DOI: 10.3390/ijms23179933 -
Journal of Lipid Research Dec 2002Pancreatic triglyceride lipase (PTL) and its protein cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar... (Review)
Review
Pancreatic triglyceride lipase (PTL) and its protein cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. PLRP1 has no known activity. PTL and PLRP2 differ in substrate specificity, behavior in bile salts and dependence on colipase. Each protein has a globular amino-terminal (N-terminal) domain, which contains the catalytic site for PTL and PLRP2, and a beta-sandwich carboxyl-terminal (C-terminal) domain, which includes the predominant colipase-binding site for PTL. Inactive and active conformations of PTL have been described. They differ in the position of a surface loop, the lid domain, and of the beta5-loop. In the inactive conformation, the lid covers the active site and, upon activation by bile salt micelles and colipase or by lipid-water interfaces, the lid moves dramatically to open and configure the active site. After the lid movement, PTL and colipase create a large hydrophobic plateau that can interact with the lipid-water interface. A hydrophobic surface loop in the C-terminal domain, the beta5' loop, may also contribute to the interfacial-binding domain of the PTL-colipase complex.
Topics: Animals; Bile Acids and Salts; Colipases; Humans; Lipase; Pancreas; Protein Structure, Tertiary
PubMed: 12454260
DOI: 10.1194/jlr.r200012-jlr200 -
Journal of Lipid Research Feb 1992The lipase superfamily includes three vertebrate and three invertebrate (dipteran) proteins that show significant amino acid sequence similarity to one another. The... (Review)
Review
The lipase superfamily includes three vertebrate and three invertebrate (dipteran) proteins that show significant amino acid sequence similarity to one another. The vertebrate proteins are lipoprotein lipase (LPL), hepatic lipase (HL), and pancreatic lipase (PL). The dipteran proteins are Drosophila yolk proteins 1, 2, and 3. We review the relationships among these proteins that have been established according to gene structural relatedness and introduce our findings on the phylogenetic relationships, distance relationships, and evolutionary history of the lipase gene superfamily. Drosophila yolk proteins contain a 104 amino acid residue segment that is conserved with respect to the lipases. We have used the yolk proteins as an outgroup to root a phylogeny of the lipase family. Our phylogenetic reconstruction suggests that ancestral PL diverged earlier than HL and LPL, which share a more recent root. Human and bovine LPL are shown to be more closely related to murine LPL than to guinea pig LPL. A comparison of the distance (a measure of the number of substitutions between sequences) between mammalian and avian LPL reveals that guinea pig LPL has the largest distance from the other mammals. Human, rodent, and rabbit HL show marked divergence from one another, although they have similar relative rates of amino acid substitution when compared to human LPL as an outgroup. Human and porcine PL are not as divergent as human and rat HL, suggesting that PL is more conserved than HL. However, canine PL demonstrates an unusually rapid rate of substitution with respect to the other pancreatic lipases. The lipases share several structurally conserved features. One highly conserved sequence (Gly-Xaa-Ser-Xaa-Gly) contains the active site serine. This feature, which agrees with that found in serine esterases and proteases, is found within the entire spectrum of lipases, including the evolutionarily unrelated prokaryotic lipases. We review the location and possible activity of putative lipid binding domains. We have constructed a conservation index (CI) to display conserved structural features within the lipase gene family, a CI of 1.0 signifying perfect conservation. We have found a correlation between a high CI and the position of conserved functional structures. The putative lipid-binding domains of LPL and HL, the disulfide-bridging cysteine residues, catalytic residues, and N-linked glycosylation sites of LPL, HL, and PL all lie within regions having a CI of 0.8 or higher. A number of amino acid substitutions have been identified in familial hyperchylomicronemia which result in loss of LPL function.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Amino Acid Sequence; Animals; Biological Evolution; Humans; Lipase; Molecular Sequence Data; Multigene Family; Sequence Alignment
PubMed: 1569370
DOI: No ID Found -
International Journal of Molecular... Jan 2023Lipases are extensively utilized industrial biocatalysts that play an important role in various industrial and biotechnological applications. Herein, polyacrylonitrile...
Lipases are extensively utilized industrial biocatalysts that play an important role in various industrial and biotechnological applications. Herein, polyacrylonitrile (PAN) was treated with hexamethylene diamine (HMDA) and activated by glutaraldehyde, then utilized as a carrier support for lipase. In this regard, the morphological structure of modified PAN before and after the immobilization process was evaluated using FTIR and SEM analyses. The immobilized lipase exhibited the highest activity at pH 8.0, with an immobilization yield of 81% and an activity of 91%. The optimal pH and temperature for free lipase were 7.5 and 40 °C, while the immobilized lipase exhibited its optimal activity at a pH of 8.0 and a temperature of 50 °C. After recycling 10 times, the immobilized lipase maintained 76% of its activity and, after 15 reuses, it preserved 61% of its activity. The lipase stability was significantly improved after immobilization, as it maintained 76% of its initial activity after 60 days of storage. The calculated Km values were 4.07 and 6.16 mM for free and immobilized lipase, and the Vmax values were 74 and 77 μmol/mL/min, respectively. These results demonstrated that synthetically modified PAN is appropriate for immobilizing enzymes and has the potential for commercial applications.
Topics: Lipase; Enzymes, Immobilized; Enzyme Stability; Candida; Temperature; Hydrogen-Ion Concentration
PubMed: 36768290
DOI: 10.3390/ijms24031970 -
Annual Review of Food Science and... Mar 2023Lipids are a large group of essential nutrients in daily diets that provide energy and maintain various physiological functions. As the global population is rapidly... (Review)
Review
Lipids are a large group of essential nutrients in daily diets that provide energy and maintain various physiological functions. As the global population is rapidly expanding, there is an urgent need to enhance the production and quality of food lipids. The development of modern biotechnology allows the manipulation of oil production in plants and microorganisms and the improvement of the nutritional value of food lipids. Various metabolic engineering strategies have been exploited to increase oil production and produce value-added oils in traditional oil crops and other novel lipid sources (e.g., plant vegetative tissues, microalgae, and oleaginous microorganisms). Furthermore, natural lipid structures can be modified by lipases to prepare functional lipids, e.g., diacylglycerols, medium-long-medium-type structured triacylglycerols, human milk-fat substitutes, and structuralphospholipids, for specific nutritional demands. In this review, we focus on the recent advances in metabolic engineering of lipid production in plants and microorganisms, and the preparation of functional lipids via biocatalysis.
Topics: Humans; Triglycerides; Oils; Biotechnology; Lipase
PubMed: 36696571
DOI: 10.1146/annurev-food-060721-024353 -
International Journal of Molecular... Feb 2022The ability of lipases to display activity beyond their physiological reactions, so-called "catalytic promiscuity", has gained increasing interest in the last two... (Review)
Review
The ability of lipases to display activity beyond their physiological reactions, so-called "catalytic promiscuity", has gained increasing interest in the last two decades as an important tool for expanding the application of these enzymes in organic synthesis. Some lipases have been shown to be effective in catalyzing a variety of C-C bond formation reactions and most of the investigations have been directed to the optimization of the products yield through a careful tuning of the experimental parameters. Despite the fact that new stereogenic carbons are formed in many of the tested reactions, the target products have been often obtained in racemic form and examples of an efficient asymmetric induction by the used lipases are quite limited. The aim of this review, mainly focused on those lipase-catalyzed promiscuous reactions in which optically active products have been obtained, is to offer a current state of art together with a perspective in this field of asymmetric synthesis.
Topics: Catalysis; Lipase
PubMed: 35269815
DOI: 10.3390/ijms23052675 -
Journal of Lipid Research Aug 2002Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries. In humans, the enzyme is mostly... (Review)
Review
Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries. In humans, the enzyme is mostly bound onto heparan-sulfate proteoglycans at the surface of hepatocytes and also of sinusoid endothelial cells. HL shares a number of functional domains with lipoprotein lipase and with other members of the lipase gene family. It is a secreted glycoprotein, and remodelling of the N-linked oligosaccharides appears to be crucial for the secretion process, rather than for the acquisition of the catalytic activity. HL is also present in adrenals and ovaries, where it might promote delivery of lipoprotein cholesterol for steroidogenesis. However, evidence of a local synthesis is still controversial. HL activity is fairly regulated according to the cell cholesterol content and to the hormonal status. Coordinate regulations have been reported for both HL and the scavenger-receptor B-I, suggesting complementary roles in cholesterol metabolism. However, genetic variants largely contribute to HL variability and their possible impact in the development of a dyslipidemic phenotype, or in a context of insulin-resistance, is discussed.
Topics: Amino Acid Sequence; Animals; Gene Expression Regulation, Enzymologic; Humans; Lipase; Liver; Molecular Sequence Data; Polymorphism, Genetic; Sequence Homology, Amino Acid; Structure-Activity Relationship
PubMed: 12177160
DOI: No ID Found -
BMC Biotechnology Nov 2021Lipases are triacylglycerol hydrolases that catalyze hydrolysis, esterification, interesterification, and transesterification reactions. These enzymes are targets of...
Lipases are triacylglycerol hydrolases that catalyze hydrolysis, esterification, interesterification, and transesterification reactions. These enzymes are targets of several industrial and biotech applications, such as catalysts, detergent production, food, biofuels, wastewater treatment, and others. Microbial enzymes are preferable for large scale production due to ease of production and extraction. Several studies have reported that lipases from filamentous fungi are predominantly extracellular and highly active. However, there are many factors that interfere with enzyme production (pH, temperature, medium composition, agitation, aeration, inducer type, and concentration, etc.), making control difficult and burdening the process. This work aimed to optimize the lipase production of four fungal isolates from oily residues (Penicillium sp., Aspergillus niger, Aspergillus sp., and Aspergillus sp.). The lipase-producing fungi isolates were morphologically characterized by optical and scanning electron microscopy. The optimal lipase production time curve was previously determined, and the response variable used was the amount of total protein in the medium after cultivation by submerged fermentation. A complete factorial design 3 was performed, evaluating the temperatures (28 °C, 32 °C, and 36 °C) and soybean oil inducer concentration (2%, 6%, and 10%). Each lipase-producing isolate reacted differently to the conditions tested, the Aspergillus sp. F18 reached maximum lipase production, compared to others, under conditions of 32 °C and 2% of oil with a yield of 11,007 (µg mL). Penicillium sp. F04 achieved better results at 36 °C and 6% oil, although for Aspergillus niger F16 was at 36 °C and 10% oil and Aspergillus sp. F21 at 32 °C and 2% oil. These results show that microorganisms isolated from oily residues derived from environmental sanitation can be a promising alternative for the large-scale production of lipases.
Topics: Aspergillus niger; Biofuels; Esterification; Lipase; Oils
PubMed: 34758800
DOI: 10.1186/s12896-021-00724-4 -
Biochimie Mar 2021Microbial lipases are most broadly used biocatalysts for environmental and industrial applications. Lipases catalyze the hydrolysis and synthesis of long acyl chain... (Review)
Review
Microbial lipases are most broadly used biocatalysts for environmental and industrial applications. Lipases catalyze the hydrolysis and synthesis of long acyl chain esters and have a characteristic folding pattern of α/β hydrolase with highly conserved catalytic triad (Serine, Aspartic/Glutamic acid and Histidine). Mesophilic lipases (optimal activity in neutral pH range, mesophilic temperature range, atmospheric pressure, normal salinity, non-radio-resistant, and instability in organic solvents) have been in use for many industrial biotransformation reactions. However, lipases from extremophiles can be used to design biotransformation reactions with higher yields, less byproducts or useful side products and have been predicted to catalyze those reactions also, which otherwise are not possible with the mesophilic lipases. The extremophile lipase perform activity at extremes of temperature, pH, salinity, and pressure which can be screened from metagenome and de novo lipase design using computational approaches. Despite structural similarity, they exhibit great diversity at the sequence level. This diversity is broader when lipases from the bacterial, archaeal, plant, and animal domains/kingdoms are compared. Furthermore, a great diversity of novel lipases exists and can be discovered from the analysis of the dark matter - the unexplored nucleotide/metagenomic databases. This review is an update on extremophilic microbial lipases, their diversity, structure, and classification. An overview on novel lipases which have been detected through analysis of the genomic dark matter (metagenome) has also been presented.
Topics: Enzyme Stability; Extremophiles; Hydrogen-Ion Concentration; Lipase; Metagenomics; Substrate Specificity; Temperature
PubMed: 33421499
DOI: 10.1016/j.biochi.2020.12.027 -
International Journal of Molecular... Dec 2015Biocatalysis offers an alternative approach to conventional chemical processes for the production of single-isomer chiral drugs. Lipases are one of the most used enzymes... (Review)
Review
Biocatalysis offers an alternative approach to conventional chemical processes for the production of single-isomer chiral drugs. Lipases are one of the most used enzymes in the synthesis of enantiomerically pure intermediates. The use of this type of enzyme is mainly due to the characteristics of their regio-, chemo- and enantioselectivity in the resolution process of racemates, without the use of cofactors. Moreover, this class of enzymes has generally excellent stability in the presence of organic solvents, facilitating the solubility of the organic substrate to be modified. Further improvements and new applications have been achieved in the syntheses of biologically active compounds catalyzed by lipases. This review critically reports and discusses examples from recent literature (2007 to mid-2015), concerning the synthesis of enantiomerically pure active pharmaceutical ingredients (APIs) and their intermediates in which the key step involves the action of a lipase.
Topics: Animals; Biocatalysis; Chemistry Techniques, Synthetic; Enzyme Stability; Esterification; Humans; Hydrolysis; Lipase; Pharmaceutical Preparations
PubMed: 26690428
DOI: 10.3390/ijms161226191