Monoterpene hydroxylation with an artificial self-sufficient P450 utilizing a P450SMO reductase domain for the electron transfer

Luan, Zheng-Jiao; Yin, Yue-Cai; Li, Ai‐Tao; Yu, Hui‐Lei; Xu, Jian‐He

doi:10.1016/j.molcatb.2015.02.006

Cited by 5 publications

(1 citation statement)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hudnik-Plevnik (1978) reportan la hidroxilación de la progesterona utilizando el micelio del hongo Rhizopus nigricans como biocatalizador y establecen las condiciones en las que se lleva a cabo la bioconversión. Luan et al (2015) mediante Ingeniería Genética, llevaron a cabo la hidroxilación de terpenos expresando el Citocromo P450 de la bacteria…”

Section: Bioconversiónunclassified

Estudio cinético de la bioconversión de naringenina

Martínez

View full text Add to dashboard Cite

Section: Bioconversiónunclassified

Estudio cinético de la bioconversión de naringenina

Martínez

View full text Add to dashboard Cite

Discovery and Engineering of Bacterial (−)‐Isopiperitenol Dehydrogenases to Enhance (−)‐Menthol Precursor Biosynthesis

et al. 2021

View full text Add to dashboard Cite

Microbial synthesis of (−)‐menthol, a compound of plant origin, is of great importance because of the high demand for this product and related sustainability issues. However, the total biosynthesis of (−)‐menthol from easily available feedstocks like (−)‐limonene by engineered microbial hosts is stalled by the poor protein expression or activity of several enzymes from the native (−)‐menthol biosynthesis pathway of mint (Mentha piperita). Among these unsatisfied steps, (−)‐isopiperitenol dehydrogenase (IPDH) catalyzed oxidation reaction of (−)‐trans‐isopiperitenol was one of the bottlenecks that need to be optimized. In this work, two novel bacterial enzymes with IPDH activity were discovered to replace their inefficient counterpart from plant cells in microbial (−)‐menthol synthesis. Two key residues in PaIPDH from Pseudomonas aeruginosa were mutated to PaIPDHE95F/Y199V with 4.4‐fold improved specific activity than PaIPDH. The mechanism for the beneficial mutations was elucidated by molecular dynamics simulations. PaIPDHE95F/Y199V was used to synthesize (−)‐isopiperitenone from (−)‐limonene in vivo via a self‐sufficient cofactor cascade enzyme reaction, affording a 3.7‐fold enhanced titer of (−)‐isopiperitenone compared with that obtained using the original mint IPDH (MpIPDH). The bacterial enzyme PaIPDHE95F/Y199V can be applied in the future for constructing a more efficient artificial pathway to biosynthesize (−)‐menthol in a microbial whole‐cell system.

show abstract

Oxygenating Biocatalysts for Hydroxyl Functionalisation in Drug Discovery and Development

Charlton

Hayes

2022

ChemMedChem

View full text Add to dashboard Cite

CÀ H oxyfunctionalisation remains a distinct challenge for synthetic organic chemists. Oxygenases and peroxygenases (grouped here as "oxygenating biocatalysts") catalyse the oxidation of a substrate with molecular oxygen or hydrogen peroxide as oxidant. The application of oxygenating biocatalysts in organic synthesis has dramatically increased over the last decade, producing complex compounds with potential uses in the pharmaceutical industry. This review will focus on hydroxyl functionalisation using oxygenating biocatalysts as a tool for drug discovery and development. Established oxygenating biocatalysts, such as cytochrome P450s and flavin-dependent monooxygenases, have widely been adopted for this purpose, but can suffer from low activity, instability or limited substrate scope. Therefore, emerging oxygenating biocatalysts which offer an alternative will also be covered, as well as considering the ways in which these hydroxylation biotransformations can be applied in drug discovery and development, such as latestage functionalisation (LSF) and in biocatalytic cascades.

show abstract

Monoterpene hydroxylation with an artificial self-sufficient P450 utilizing a P450SMO reductase domain for the electron transfer

Cited by 5 publications

References 22 publications

Estudio cinético de la bioconversión de naringenina

Estudio cinético de la bioconversión de naringenina

Discovery and Engineering of Bacterial (−)‐Isopiperitenol Dehydrogenases to Enhance (−)‐Menthol Precursor Biosynthesis

Oxygenating Biocatalysts for Hydroxyl Functionalisation in Drug Discovery and Development

Contact Info

Product

Resources

About