Guangzheng Wei

Bio: Guangzheng Wei is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Heterologous expression & Ergoline. The author has an hindex of 1, co-authored 3 publications receiving 8 citations.

Catalase Involved in Oxidative Cyclization of the Tetracyclic Ergoline of Fungal Ergot Alkaloids.

Abstract: A dedicated enzyme for the formation of the central C ring in the tetracyclic ergoline of clinically important ergot alkaloids has never been found. Herein, we report a dual role catalase (EasC), unexpectedly using O2 as the oxidant, that catalyzes the oxidative cyclization of the central C ring from a 1,3-diene intermediate. Our study showcases how nature evolves the common catalase for enantioselective C-C bond construction of complex polycyclic scaffolds.

Biosynthesis and synthetic biology of psychoactive natural products.

Abstract: Psychoactive natural products play an integral role in the modern world. The tremendous structural complexity displayed by such molecules confers diverse biological activities of significant medicinal value and sociocultural impact. Accordingly, in the last two centuries, immense effort has been devoted towards establishing how plants, animals, and fungi synthesize complex natural products from simple metabolic precursors. The recent explosion of genomics data and molecular biology tools has enabled the identification of genes encoding proteins that catalyze individual biosynthetic steps. Once fully elucidated, the "biosynthetic pathways" are often comparable to organic syntheses in elegance and yield. Additionally, the discovery of biosynthetic enzymes provides powerful catalysts which may be repurposed for synthetic biology applications, or implemented with chemoenzymatic synthetic approaches. In this review, we discuss the progress that has been made toward biosynthetic pathway elucidation amongst four classes of psychoactive natural products: hallucinogens, stimulants, cannabinoids, and opioids. Compounds of diverse biosynthetic origin - terpene, amino acid, polyketide - are identified, and notable mechanisms of key scaffold transforming steps are highlighted. We also provide a description of subsequent applications of the biosynthetic machinery, with an emphasis placed on the synthetic biology and metabolic engineering strategies enabling heterologous production.

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

Abstract: Alkaloids are a group of natural products with interesting pharmacological properties and a long history of medicinal application. Their complex molecular structures have fascinated chemists for decades, and their total synthesis still poses a considerable challenge. In a previous review, we have illustrated how biocatalysis can make valuable contributions to the asymmetric synthesis of alkaloids. The chemo-enzymatic strategies discussed therein have been further explored and improved in recent years, and advances in amine biocatalysis have vastly expanded the opportunities for incorporating enzymes into synthetic routes towards these important natural products. The present review summarises modern developments in chemo-enzymatic alkaloid synthesis since 2013, in which the biocatalytic transformations continue to take an increasingly ‘central’ role.

Biosynthesis, total synthesis, and biological profiles of Ergot alkaloids.

Abstract: While the use of ergot alkaloids in folk medicine has been practiced for millennia, systematic investigations on their therapeutic potential began about 100 years ago. Subsequently, Albert Hofmann's discovery of lysergic acid diethylamide (LSD) and its intense psychedelic properties garnered worldwide attention and prompted further studies of this compound class. As a result, several natural ergot alkaloids were discovered and unnatural analogs were synthesized, and some were used to treat an array of maladies, including Alzheimer's and Parkinson's disease. While LSD was never commercially approved, recent clinical studies have found it can be an innovative and effective treatment option for several psychiatric disorders. Ongoing biosynthetic and total synthetic investigations aim to understand the natural origins of ergot alkaloids, help develop facile means to produce these natural products and enable their continued use as medicinal chemistry lead structures. This review recounts major developments over the past 20 years in biosynthetic, total synthetic, and pharmaceutical studies. Many ergot alkaloid biosynthetic pathways have been elucidated, with some of them subsequently applied toward "green" syntheses. New chemical methodologies have fostered a fast and efficient access to the ergoline scaffold, prompting some groups to investigate biological properties of natural product-like ergot alkaloids. Limited pharmaceutical applications have yet to completely bypass the undesirable side effects of ergotism, suggesting further studies of this drug class are likely needed and will potentially harness major therapeutic significance.