Amaryllidaceae Alkaloids and Isoquinoline Alkaloids: A Perspective on Historical Approaches to Pathway Elucidation

Metabolomic and transcriptomic analyses reveal the monoterpenoid indole alkaloid biosynthesis in Neolamarckia cadamba

Findings reveal tissue-specific metabolite accumulation and key genes involved in MIA biosynthesis in N. cadamba that provide valuable insights into specialized metabolism and establish a foundation for future metabolic engineering and functional genomics studies.

Transcriptomic landscape of Cestrum diurnum: elucidating pathways of medicinally important terpenoids and toxic alkaloids

From botanical origins to modern laboratories: 50 year journey in protoberberine alkaloid total synthesis.

Covering: up to 2025Protoberberine alkaloids (PBs) and tetrahydroprotoberberine alkaloids (THPBs) exhibit diverse pharmacological activities, driving significant interest in their efficient synthesis. This review systematically categorizes recent advances in the total synthesis of these alkaloids based on core-ring-closure strategies. For protoberberines, key methodologies include transition-metal-catalyzed coupling, C-H activation, Mannich/Friedel-Crafts reactions, and tandem cyclizations, enabling the rapid construction of the tetracyclic skeleton. In chiral THPB synthesis, asymmetric strategies, such as chiral auxiliaries, organocatalysis, and transition-metal-catalyzed asymmetric reactions, address the stereochemical challenges at the C14 position. Enzymatic and chemoenzymatic approaches further complement chemical synthesis by enhancing stereocontrol and sustainability. By critically analyzing the efficiency, scope, and limitations of existing strategies, this review highlights innovations in reaction design and underscores the importance of modular, catalytic, and bio-inspired methods for future alkaloid synthesis.

Chalcone Synthase: From Discovery to Biotechnological Applications.

Flavonoids, a class of phenolic compounds widely distributed throughout the plant kingdom, exhibit extensive physiological and pharmacological properties. Chalcone synthase (CHS), the key and rate-limiting gateway enzyme in flavonoid biosynthesis, catalyzes the condensation reaction between malonyl-CoA and p-coumaroyl-CoA to produce chalcone, the core C6-C3-C6 skeleton of flavonoids and related secondary metabolites. This review systematically summarizes the current knowledge of CHS, focusing on its protein structure, catalytic mechanism, evolutionary origin, and divergence patterns. It further elaborates on the precisely orchestrated multilayered regulation of CHS, including tissue-specific and developmental transcription mediated by MYB, bHLH, and WD40 transcription factors, responses to key environmental cues (light and biotic/abiotic stress stimuli), and post-translational modifications (ubiquitination and phosphorylation) that modulate its stability and catalytic activity. Additionally, targeted rational design and metabolic engineering strategies (gene-directed evolution, heterologous expression, pathway optimization) to efficiently enhance CHS performance in microbial and plant cell factories for boosted flavonoid production are summarized. This comprehensive analysis provides a solid theoretical and practical basis for optimizing CHS function and flavonoid biosynthesis, facilitating the sustainable development and practical implementation of industrial and agricultural applications of these bioactive compounds.

A Comprehensive Review on the Biosynthesis of Tropane Alkaloids

Tropane alkaloids (TA) constitute a class of plant specialized metabolites with important pharmaceutical applications, including the anticholinergic agents hyoscyamine and scopolamine and the local anesthetic cocaine. Over the past decade, advances in genomics, structural biology, and synthetic biology have substantially revised our understanding of TA biosynthesis, leading to the identification of numerous key biosynthetic enzymes and evolutionary mechanisms. This review comprehensively summarizes current knowledge of TA biosynthesis from precursor formation to structurally diverse end products. We describe the pathway from putrescine to tropinone, the stereoselective metabolic branching mediated by Tropinone Reductases, and the downstream biosynthesis of medicinal tropane alkaloids, calystegines, and cocaine. Particular emphasis is placed on recent discoveries concerning catalytic mechanisms, structural determinants of substrate specificity, metabolic compartmentalization, and the convergent evolution of TA biosynthesis in Solanaceae and Erythroxylaceae. We further integrate advances in genomics, evolutionary biology, and metabolic engineering to highlight emerging strategies for microbial production and pathway redesign. By providing a comprehensive synthesis of recent progress and critical perspectives on unresolved questions, this review offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering.

Glycyrrhiza inflata O-methyltransferases characterization for one-step production of trimethyl myricetin/dihydromyricetin.

Flavonoids are plant specialized metabolites widely distributed in plants with many health benefits. O-methyltransferases (OMTs) are pivotal in plant specialized metabolism by producing methylated derivatives with enhanced biological activity. In this study, we identified two novel flavonoid OMTs, GiOMT4 and GiOMT9, from Glycyrrhiza inflata, a medicinal licorice species commonly used in Chinese medicine. These enzymes could catalyze myricetin and dihydromyricetin to produce 3',4',5'-O-trimethyl derivatives in a reaction. Structural modeling and site-directed mutagenesis identified Trp193 as critical residue determining the specificity of trimethylation of GiOMT4. Notably, trimethylation markedly enhanced the antibacterial activity of flavonoids against Gram-positive bacteria, including Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus. Furthermore, trimethyl dihydromyricetin was identified as a novel compound with unexplored pharmacological potential. Collectively, this study expands the enzymatic repertoire of licorice OMTs, provides new insights into the structure-function relationships underling multiple methylations, and establishes a foundation or sustainable biocatalytic production of highly bioactive methylated flavonoids in G. inflata and related species.