Herein, we report a biocatalytic approach to synthesize plant tetrahydroisoquinoline alkaloids (THIQAs) from dihydroisoquinoline (DHIQ) precursors using imine reductases and -methyltransferase (NMT). The imine reductase IR45 was engineered to significantly expand its substrate specificity, enabling efficient and stereoselective conversion of 1-phenyl and 1-benzyl 6,7-dimethoxy-DHIQs into the corresponding ()-tetrahydroisoquinolines (-THIQs). Coclaurine -methyltransferase (CNMT) was able to further efficiently convert these ()-THIQ intermediates into ()-THIQAs. By assembling IRED, CNMT, and glucose dehydrogenase (GDH) in one reaction, we effectively constituted two artificial biosynthetic pathways in and successfully applied them to the production of five ()-THIQAs. This highly efficient (100% yield from DHIQs) and easily tailorable (adding other genes) biosynthetic approach will be useful for producing a variety of plant THIQAs.
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http://dx.doi.org/10.1039/c9sc03773j | DOI Listing |
Bioorg Med Chem
November 2024
Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China. Electronic address:
The emergence of multidrug resistance (MDR) in malignant tumors is one of the major threats encountered currently by many chemotherapeutic agents. Among the various mechanisms involved in drug resistance, P-glycoprotein (P-gp, ABCB1), a member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells, and the metabolic enzyme CYP1B1 are widely considered to be two critical targets for overcoming MDR. Unfortunately, no MDR modulator has been approved by the FDA to date.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China; College of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China. Electronic address:
Molecules
September 2024
State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, CAS Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Bioorg Chem
December 2024
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Evin, 1983963113 Tehran, Iran. Electronic address:
Noscapine, a tetrahydroisoquinoline alkaloid, was first isolated from Papaver somniferum and identified by Rabiquet in 1817. It has been used as an anti-tussive agent since the mid-1950 s. After the discovery of its anti-mitotic potential, it was into the limelight once again.
View Article and Find Full Text PDFJ Agric Food Chem
September 2024
Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt.
Three new series of 3-(substituted)methylthio-4-cyano-5,6,7,8-tetrahydroisoquinolines were designed and synthesized starting from readily available materials, 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(4-pyridyl, 3-pyridyl, phenyl, 4-methoxyphenyl, or 4-chlorophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2)-thiones - in high yields and very pure states. Thus, compounds - were reacted with some chloro reagents, namely, -aryl-2-chloroacetamides - and -(naphthalen-2-yl)-2-chloroacetamide () under mild basic conditions to give the first two series of the target compounds, 3-(-aryl)carbamoylmethylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles - and -, respectively. Reaction of compounds , with ethyl chloroacetate under the same conditions gave the other series, 3-ethoxycarbonyl-methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles ,.
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