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De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.
Nat Commun
October 2024
Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, SE-412 96, Gothenburg, Sweden.
Protoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of plant-specialized natural metabolites with many pharmacological properties. Microbial biosynthesis has been allowed for accessibility and scalable production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de novo produce a series of protoberberines and BZDAs, including palmatine, berberine, chelerythrine, sanguinarine and chelirubine.
View Article and Find Full Text PDFGouregine, an -Gem-Dimethyltetradehydrocularine Alkaloid, and Other Aporphinoid Alkaloids from the Bark of (Annonaceae) and Their In Vitro Cytotoxic Activities.
Molecules
August 2024
Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, BA, Brazil.
R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará.
View Article and Find Full Text PDFPotentiation of prefrontal cortex dopamine function by the novel cognitive enhancer d-govadine.
Neuropharmacology
March 2024
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. Electronic address:
Cognitive impairment is a debilitating feature of psychiatric disorders including schizophrenia, mood disorders and substance use disorders for which there is a substantial lack of effective therapies. d-Govadine (d-GOV) is a tetrahydroprotoberberine recently shown to significantly enhance working memory and behavioural flexibility in several prefrontal cortex (PFC)-dependent rodent tasks. d-GOV potentiates dopamine (DA) efflux in the mPFC and not the nucleus accumbens, a unique pharmacology that sets it apart from many dopaminergic drugs and likely contributes to its effects on cognitive function.
View Article and Find Full Text PDFAn Enzymatic Strategy for the Selective Methylation of High-Value-Added Tetrahydroprotoberberine Alkaloids.
Int J Mol Sci
October 2023
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Tetrahydroprotoberberines (THPBs) are plant-specific alkaloids with significant medicinal value. They are present in trace amounts in plants and are difficult to chemically synthesize due to stereoselectivity and an unfavorable environment. In this study, a selective methylation strategy was developed for the biocatalysis of seven high-value-added THPB compounds using 4'--methyltransferase (), norcoclaurine 6--methyltransferase (), and ()-scoulerine 9--methyltransferase ( and ) in engineered .
View Article and Find Full Text PDFMorphine Withdrawal-Induced Hyperalgesia in Models of Acute and Extended Withdrawal Is Attenuated by -Tetrahydropalmatine.
Int J Mol Sci
May 2023
Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 2A1, Canada.
Effective pain control is an underappreciated aspect of managing opioid withdrawal, and its absence presents a significant barrier to successful opioid detoxification. Accordingly, there is an urgent need for effective non-opioid treatments to facilitate opioid detoxification. -Tetrahydropalmatine (-THP) possesses powerful analgesic properties and is an active ingredient in botanical formulations used in Vietnam for the treatment of opioid withdrawal syndrome.
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