The Impact of Amine-Functionalised Iron Oxide Nanoparticles on the Menaquinone-7 Isomer Profile and Production of the Bioactive Isomer

Neha Lal; Mostafa Seifan; Alireza Ebrahiminezhad; Aydin Berenjian

doi:10.1007/s12033-023-00832-w

The Impact of Amine-Functionalised Iron Oxide Nanoparticles on the Menaquinone-7 Isomer Profile and Production of the Bioactive Isomer

Mol Biotechnol. 2023 Jul 30. doi: 10.1007/s12033-023-00832-w. Online ahead of print.

Authors

Neha Lal¹, Mostafa Seifan¹, Alireza Ebrahiminezhad², Aydin Berenjian^{3

4}

Affiliations

¹ School of Engineering, The University of Waikato, Hamilton, 3240, New Zealand.
² Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
³ School of Engineering, The University of Waikato, Hamilton, 3240, New Zealand. aydin.berenjian@colostate.edu.
⁴ Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO, 80523, USA. aydin.berenjian@colostate.edu.

PMID: 37517081
DOI: 10.1007/s12033-023-00832-w

Abstract

The K family of vitamins includes a collection of molecules with different pharmacokinetic characteristics. Menaquinone-7 (MK-7) has the finest properties and is the most therapeutically beneficial due to its long plasma half-life and outstanding extrahepatic bioavailability. MK-7 exhibits cis-trans isomerism, and merely the all-trans form is biologically efficacious. Therefore, the remedial value of MK-7 end products is exclusively governed by the quantity of all-trans MK-7. Consumers favour fermentation for the production of MK-7; however, it involves several challenges. The low MK-7 yield and extensive downstream processing requirements increase production costs, resulting in an expensive final product that is not universally available. Bacterial cell immobilisation with iron oxide nanoparticles (IONs) can potentially address the limitations of MK-7 fermentation. Uncoated IONs tend to have low stability and can adversely affect cell viability; thus, amine-functionalised IONs, owing to their increased physicochemical stability and biocompatibility, are a favourable alternative. Nonetheless, employing biocompatible IONs for this purpose is only advantageous if the bioactive MK-7 isomer is obtained in the most significant fraction, exploring which formed the aim of this investigation. Two amine-functionalised IONs, namely 3-aminopropyltriethoxysilane (APTES)-coated IONs (IONs@APTES) and L-Lysine (L-Lys)-coated IONs (L-Lys@IONs), were synthesised and characterised, and their impact on various parameters was evaluated. IONs@APTES were superior, and the optimal concentration (300 [Formula: see text]g/mL) increased all-trans MK-7 production and improved its yield relative to the untreated cells by 2.3- and 3.1-fold, respectively. The outcomes of this study present an opportunity to develop an innovative and effective fermentation method that enhances the production of bioactive MK-7.

Keywords: 3-Aminopropyltriethoxysilane; Bacterial cell immobilisation; Biocompatible iron oxide nanoparticles; Fermentation; L-Lysine; Menaquinone-7 isomers.