Selective hydroxylation of 1,8- and 1,4-cineole using bacterial P450 variants

Lee, Joel H. Z.; Wong, Siew Hoon; Stok, Jeanette E.; Bagster, Sarah A; Beckett, J. C.; Clegg, Jack K.; Brock, Aidan J.; Voss, James J. De; Bell, Stephen

doi:10.1016/j.abb.2018.12.025

Cited by 11 publications

(11 citation statements)

References 99 publications

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“…In turn, the variant F87W/Y96F/L244A/V247A (WFAL) made it possible to obtain 5α-hydroxy-1,8-cineole as the main product (88%, ee = 86% (1 S )). Additionally, 10% of 6α-hydroxy-1,8-cineole and 2% of 5β-hydroxy-1,8-cineole were formed [ 105 ].…”

Section: Eucalyptol Biotransformationmentioning

confidence: 99%

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Can Eucalyptol Replace Antibiotics?

et al. 2021

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One of the primary reasons for the search for new antimicrobial agents is the increasing and spreading resistance of microorganisms to previously used drugs. This is particularly important in the case of rapidly progressing infections that require the rapid administration of an appropriately selected antibiotic. However, along with the administration of antibiotics, complications in the disease-weakened body may arise in the form of systemic mycoses, viral infections, and protozoan infections. Therefore, there is an increasing interest among researchers focusing on the use of naturally occurring terpenic compounds in stand-alone or combined therapies with antibiotics. In this publication, the aim of our work is to present the results of a literature review on the antimicrobial activity of eucalyptol.

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Section: Eucalyptol Biotransformationmentioning

confidence: 99%

“…The CYP102A1 mutant RLYFGVQ generated 6α-hydroxy-1,8-cineole as the sole product (>98%). The RLYFAIP variant, on the other hand, was less selective for the oxidation of 1,8-cineol, generating significant amounts of 5α-hydroxy-1,8-cineole in addition to the main product, 6α-hydroxy-1,8-cineole [ 105 ].…”

Section: Eucalyptol Biotransformationmentioning

confidence: 99%

Can Eucalyptol Replace Antibiotics?

et al. 2021

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“…[55] Fore xample the engineering of P450cam and P450-BM3 facilitated ashift in the selective hydroxylation of the monoterpenes 1,4-(16)and 1,8-cineole (17)inducing two stereocentres (Figure 6). [56] Multi-oxyfunctionalisation provides an additional approach exploited in biocatalysis.Awild-type P450, TxtC, is capable of both aliphatic and aromatic CÀHhydroxylation Scheme 3. Chemoenzymatic synthesis using engineered P450-BM3 variants:a)Hydroxylation enables subsequent Dess-Martin oxidation to norditerpenoid alkaloid nigelladineA(6); b) alternatively,Sonogashira reaction precedes P450 hydroxylation affording the bis-2-substituted benzofuran derivative (11).…”

Section: Hydroxylationmentioning

confidence: 99%

“… [55] For example the engineering of P450cam and P450‐BM3 facilitated a shift in the selective hydroxylation of the monoterpenes 1,4‐ ( 16 ) and 1,8‐cineole ( 17 ) inducing two stereocentres (Figure 6 ). [56] …”

Section: Oxyfunctionalisation: Nature's Manifold Ways Of Forming C−o Bondsmentioning

confidence: 99%

Enzymatic Late‐Stage Modifications: Better Late Than Never

et al. 2021

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Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late‐stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme‐catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late‐stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development.

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“…[55] Zum Beispiel erleichtern P450cam und P450-BM3 eine Verschiebung der Hydroxylierungsselektivität der Monoterpene 1,4-( 16) und 1,8-Cineol (17), wodurch zwei Stereozentren aufgebaut werden (Abbildung 6). [56] Die Multi-Oxyfunktionalisierung bietet einen zusätzlichen Ansatz, der in der Biokatalyse weit ausgeschçpft wird. Das Wildtypenzym P450 TxtC ermçglicht aliphatische sowie aromatische C-H-Hydroxylierungen in der späten Funktionalisierung eines Diketopiperazins (18).…”

Section: Hydroxylierungunclassified