Transaminase‐Catalyzed Continuous Synthesis of Biogenic Aldehydes

Abstract

The physiological role of biogenic aldehydes, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL), has been associated with cardiovascular and neurodegeneratived isorders. The availability of these substrates is limited and robust synthetic methodologies would greatly facilitate further biological studies. Herein, at ransaminase-mediated single-step process in continuous mode, which leads to excellent product yields (90-95 %), is reported. Coimmobilization of the pyridoxal phosphate (PLP) cofactor eliminated the need for exogenous addition of this reagent without affecting the longevity of the system,d elivering at ruly self-sufficient process.Aldehydes species are continuouslyg enerated in biological systemsf rom aw ide range of endo-and exogenous precursors. [1a] Biogenic aldehydes are defined as those formed endogenously through enzyme-dependento rs pontaneouso xidation of lipids, sugars,a nd primary amines. [1b-e] Thankst ot he strong electrophilicity of the terminal carbonyl group, they are considered to be the most reactive compounds between biomolecules. [2] If not metabolized, biogenic aldehydesc an become cytotoxic due to covalent modificationso ra dduct formation with proteins( typically Cys, Lys, His, and Arg residues), [3] nucleic acids( involving amino groups of both purines and pyrimidines), [4] and coenzymes, [5] with subsequent inactivation through Michael addition, Knoevenagel condensation, Schiff base, and free radical formation.M oreover,a ldehydes are relatively long-lived, so they not only reactw ith targets in their proximity,b ut can also diffuse or be transported to remote sites. [6] Although, originally,b iogenic aldehydes were believed to be innocuous intermediates predominantly formed by oxidative amination with monoamine oxidase (MAO), recent studies demonstrated that not only weret hey neurotransmitters themselves, [7] but they were also involved in the development of cardiovascular [8] and neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) [7] and played ak ey role in alcohol-related disorders. [2] Synthetically,n umerous attempts have been reportedf or the preparation of biogenic aldehydes. [9a-d] However,t hese methodologies requires everal steps, drastic reaction condi- [a] Dr.

Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades**

“…Choline oxidase activity was tested against tyrinol in the MPIR. The resulting biogenic aldehyde is a key intermediate in the biosynthesis of benzylisoquinoline alkaloids and often requires multistep syntheses [42, 43] . Despite the biooxidation proving highly efficient (120 mM substrate loading; >90 % conversion; STY: 8.37 g L −1 h −1 ; productivity: 5.1 g product g enzyme −1 ) tyramine was commercially available at a lower cost than the alcohol so this step was not necessary.…”

Enzyme immobilization inside the porous wood structure: a natural scaffold for continuous-flow biocatalysis

“…9 In these approaches, enzymes are oen coupled to powders or porous beats and subsequently randomly packed into a xed bed reactor. [10][11][12] However, such reactors have uncontrolled uid dynamics, resulting in inhomogeneous distribution of reactants and products, a broad residence time distribution, and low selectivity. 13 In addition, xed bed reactors can exhibit a high pressure drop.…”

Biocatalysis and Flow Chemistry: Artificial Cell Factories

“…In collaboration with Dr. Lopez-Gallego (San Sebastian, Spain), we have also worked on the co-immobilisation of PLP and HeWT which has led to the assembly of fully self-sufficient systems which performed very well in continuous flow. [18,19] As our knowledge in the field progressed, we increased the complexity of the cascade, adding a second module in the assembly. Here, the amine to aldehyde/ketone catalysis was followed by a second reactor to perform the reduction to alcohol.…”