Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route.

Chem Sci

State Key Laboratory of Microbial Metabolism , School of Life Sciences and Biotechnology , Shanghai Jiao Tong University, Shanghai 200240 , China . Email:

Published: January 2020

AI Article Synopsis

  • Researchers developed a biocatalytic method to create plant tetrahydroisoquinoline alkaloids (THIQAs) from dihydroisoquinoline (DHIQ) precursors using specific enzymes.
  • They engineered an enzyme called imine reductase IR45 to enhance its ability to convert DHIQs into ()-tetrahydroisoquinolines (-THIQs) with high efficiency and selectivity.
  • By combining multiple enzymes in one reaction, they established two artificial biosynthetic pathways to produce five different ()-THIQAs with a 100% yield, providing a versatile method for generating a range of plant THIQAs.

Article Abstract

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067268PMC
http://dx.doi.org/10.1039/c9sc03773jDOI Listing

Publication Analysis

Top Keywords

plant tetrahydroisoquinoline
8
tetrahydroisoquinoline alkaloids
8
imine reductase
8
biosynthesis plant
4
alkaloids imine
4
reductase route
4
route report
4
report biocatalytic
4
biocatalytic approach
4
approach synthesize
4

Similar Publications

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 PDF

High-throughput screening of the natural STK11 agonist dauricine: A biphenylisoquinoline alkaloid exerting anti-NSCLC effects and reversing gefitinib resistance.

Eur 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:

Article Synopsis
  • Dauricine, a natural compound derived from Menispermum dauricum, has potential as an anti-cancer agent, particularly for non-small cell lung cancer (NSCLC), by acting as a serine/threonine kinase 11 (STK11) agonist.
  • The study employed a lentiviral model to demonstrate that dauricine activates the STK11/AMPK pathway, inhibiting growth in cancer cells and enhancing the effectiveness of gefitinib, a common treatment for lung cancer.
  • Additionally, dauricine not only increases STK11 protein levels but also helps restore sensitivity to gefitinib in drug-resistant cell models, suggesting a promising avenue for improving treatment outcomes in NSCLC patients.
View Article and Find Full Text PDF

Metabolic and Pharmacokinetic Profiling Studies of N, N-Dimethylaniline-Heliamine in Rats by UHPLC-Q-Orbitrap MS/MS.

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.

Article Synopsis
  • Cardiovascular disease is the leading cause of death globally, and DH, a synthetic compound, shows promise as an antiarrhythmic agent despite limited research on its metabolic behavior in rats.
  • This study identifies 16 metabolites of DH and establishes a reliable method for measuring DH levels in rat plasma, focusing on different metabolic processes such as demethylation and glucuronidation.
  • The findings indicate that DH is well-absorbed with significant tissue distribution, having low toxicity and various excretion pathways.
View Article and Find Full Text PDF

Synthesis and modification of noscapine derivatives as promising future anticancer agents.

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 PDF

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 ,.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!