Raman spectroscopy and one-dimensional convolutional neural network modeling as a real-time monitoring tool for in vitro transaminase-catalyzed synthesis of a pharmaceutically relevant amine precursor

被引：1

作者：

Madsen, Julie osterby ^{[1
,2
]}

Topalian, Sebastian Olivier Nymann ^{[1
]}

Jacobsen, Mikkel Fog ^{[3
]}

Skovby, Tommy ^{[4
]}

Gernaey, Krist V. ^{[1
]}

Myerson, Allan S. ^{[2
]}

Woodley, John ^{[1
,5
]}

机构：

[1] Tech Univ Denmark, Dept Chem & Biochem Engn, Lyngby, Denmark

[2] MIT, Dept Chem Engn, Cambridge, MA USA

[3] H Lundbeck A S, Route Design, Proc Dev, Valby, Denmark

[4] H Lundbeck A S, Chem Prod Dev, Nykobing Sjaelland, Denmark

[5] Tech Univ Denmark, Dept Chem & Biochem Engn, DK-2800 Lyngby, Denmark

来源：

BIOTECHNOLOGY PROGRESS | 2024年 / 40卷 / 03期

关键词：

biocatalysis; chemometrics; Raman spectroscopy; real-time monitoring; transaminase; ASYMMETRIC-SYNTHESIS; BIOCATALYSIS;

D O I：

10.1002/btpr.3444

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Raman spectroscopy has been used to measure the concentration of a pharmaceutically relevant model amine intermediate for positive allosteric modulators of nicotinic acetylcholine receptor in a omega-transaminase-catalyzed conversion. A model based on a one-dimensional convolutional neural network was developed to translate raw data augmented Raman spectra directly into substrate concentrations, with which the conversion from ketone to amine by omega-transaminase could be determined over time. The model showed very good predictive capabilities, with R2 values higher than 0.99 for the spectra included in the modeling and 0.964 for an independent dataset. However, the model could not extrapolate outside the concentrations specified by the model. The presented work shows the potential of Raman spectroscopy as a real-time monitoring tool for biocatalytic reactions.

引用

页数：13