Enhancing enantioselectivity of Candida antarctica lipase B towards chiral sec-alcohols bearing small substituents through hijacking sequence of A homolog

Yi, Seonghyeon; Park, Seongsoon

doi:10.1016/j.tetlet.2021.153186

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Thus, a chiral secondary alcohol with substituents of different sizes (e.g. , methyl vs. propyl or bigger) can be sterically differentiated [ 118 ], explaining why most lipases tend to prefer R-enantiomeric secondary alcohols (Kazlauska’s rule) [ 107 ]. As will be seen ( Table 1 ), there are other factors that give rise to exceptions or different interpretations to this rule: the “Mirror-Image Packing” rule ( Figure 5 ) has broad support based on crystal structures [ 119 ] or the “Key Region(s) Influencing Enantioselectivity”(KRIE), which is based on a review of papers by its authors [ 120 ] about mutant lipases that improved their enantioselectivity not only towards derivatives of chiral alcohols but also towards those of chiral acids.…”

Section: Microbial Lipases: Structure and Functionmentioning

confidence: 99%

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

Godoy

Pardo‐Tamayo

Barbosa

2022

IJMS

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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.

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Section: Microbial Lipases: Structure and Functionmentioning

confidence: 99%

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

Godoy

Pardo‐Tamayo

Barbosa

2022

IJMS

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“…In this study, we initially aimed to discover a novel family VIII carboxylesterase through a homologous search from the protein sequence database (BLASTP), which often provides useful information to improve enzyme function by comparison to related sequences. 10 We used the protein sequence of a structurally characterized family VIII carboxylesterase (pdb code: 4IVK) as a template for homologous search. We selected eight sequences among the resulting search hits that each possesses higher than 60% sequence identity (Figure S1 and Table S1).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The enantioselectivity of PBE was determined as an enantiomeric ratio ( E , defined by Chen et al) toward the hydrolysis of a series of sec -alcohol esters including but-3-yn-2-yl esters, which is a useful building block for the synthesis of bioactive compounds and is also known as a challenging substrate to resolve (Table ). , PBE exhibited low-to-moderate enantioselectivity ( E = 1.1–10.1) toward most sec -alcohol esters except 1-phenylethyl alcohol esters ( E = 9.9 or 36.1). The errors of the calculated E values from the multiple measurements were less than 10%.…”

Section: Resultsmentioning

confidence: 99%

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Discovery and Redesign of a Family VIII Carboxylesterase with High (S)-Selectivity toward Chiral sec-Alcohols

Park

2022

ACS Catal.

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Highly enantioselective lipase has been widely utilized in the preparation of versatile enantiopure chiral secalcohols through kinetic or dynamic kinetic resolution. Lipase is intrinsically (R)-selective, and it is difficult to obtain (S)-selective lipase. Recent crystal structures of a family VIII carboxylesterase have revealed that the spatial array of its catalytic triad is the mirror image of that of lipase but with a catalytic triad that is distinct from lipase. We, therefore, hypothesized that the family VIII carboxylesterase may exhibit (S)-enantioselectivity toward secalcohols similar to (S)-selective serine protease, whose catalytic triad is also spatially arrayed as its mirror image. In this study, a homologous enzyme (carboxylesterase from Proteobacteria bacterium SG_bin9, PBE) of a known family VIII carboxylesterase (pdb code: 4IVK) was prepared, which showed not only moderate (S)selectivity toward sec-alcohols such as 3-butyn-2-ol and 1-phenylethyl alcohol but also (R)-selectivity toward particular sec-alcohols among the substrates explored. Furthermore, the (S)-selectivity of PBE has been significantly improved by rational redesign based on molecular modeling. Molecular modeling identified a binding pocket composed of Ser381, Ala383, and Arg408 for the methyl substituent of (R)-1-phenylethyl acetate and suggested that larger residues may increase the enantioselectivity by interfering with the binding of the slow-reacting enantiomer. As predicted, substituting Ser381with larger residues (Phe, Tyr, and Trp) significantly improved the (S)-selectivity of PBE toward all sec-alcohols explored, even the substrates toward which the wild-type PBE exhibits (R)-selectivity. For instance, the enantioselectivity toward 3-butyn-2-ol and 1-phenylethyl alcohol was improved from E = 5.5 and 36.1 to E = 2001 and 882, respectively, by single mutagenesis (S381F).

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“…More recently, this technology has been used to evolve metabolic pathways (Hausmann and Jaeger, 2010). Based on this technology, quite a large number of examples of directed evolution for lipase/esterase can be found (Moore and Arnold, 1996; Giver et al ., 1998; Schmidt et al ., 2004; Ivancic et al ., 2007; Schmidt et al ., 2009; Jochens et al ., 2010; Adesioye et al ., 2018; Gao et al ., 2021; Liu et al ., 2021; Yi and Park, 2021).…”

Section: Introductionmentioning

confidence: 99%

Phthalate hydrolase: distribution, diversity and molecular evolution

Bhattacharyya

Basu

Dhar

et al. 2021

Environ Microbiol Rep

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The alpha/beta-fold superfamily of hydrolases is rapidly becoming one of the largest groups of structurally related enzymes with diverse catalytic functions. In this superfamily of enzymes, esterase deserves special attention because of their wide distribution in biological systems and importance towards environmental and industrial applications. Among various esterases, phthalate hydrolases are the key alpha/beta enzymes involved in the metabolism of structurally diverse estrogenic phthalic acid esters, ubiquitously distributed synthetic chemicals, used as plasticizer in plastic manufacturing processes. Although they vary both at the sequence and functional levels, these hydrolases use a similar acid-base-nucleophile catalytic mechanism to catalyse reactions on structurally different substrates. The current review attempts to present insights on phthalate hydrolases, describing their sources, structural diversities, phylogenetic affiliations and catalytically different types or classes of enzymes, categorized as diesterase, monoesterase and diesterase-monoesterase, capable of hydrolysing phthalate diester, phthalate monoester and both respectively. Furthermore, available information on in silico analyses and sitedirected mutagenesis studies revealing structurefunction integrity and altered enzyme kinetics have been highlighted along with the possible scenario of their evolution at the molecular level.

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Enhancing enantioselectivity of Candida antarctica lipase B towards chiral sec-alcohols bearing small substituents through hijacking sequence of A homolog

Cited by 9 publications

References 39 publications

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

Discovery and Redesign of a Family VIII Carboxylesterase with High (S)-Selectivity toward Chiral sec-Alcohols

Phthalate hydrolase: distribution, diversity and molecular evolution

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