Plants are a vast reservoir of natural products with diverse structural scaffolds, making them an invaluable source for discovering novel enzymes that catalyze unique and evolutionarily specialized metabolic transformations in biosynthetic pathways. Rapid advances in genomics, metabolomics, protein structure prediction, and heterologous pathway reconstruction have enabled the identification of numerous cryptic biosynthetic enzymes responsible for key scaffold-forming and tailoring reactions in metabolism. Particularly notable are the discoveries of plant-derived enzymes that catalyze challenging chemical transformations, including oxidative carbon-carbon bond rearrangements, atypical cycloadditions, radical-mediated coupling reactions, and iterative scaffold remodeling. This review summarizes major advances in enzyme discovery in plant natural product biosynthesis in recent years, focusing on emerging catalytic mechanisms, strategies for elucidating pathways, and evolutionary relationships, and highlights their implications for synthetic biology, metabolic engineering, and the sustainable production of valuable natural products.
Zheng-Xi Zhang, Han Ke, Jin Wang et al.· Current Opinion in Chemical...· 0 citations
Antibody-drug conjugates (ADCs) represent an emerging pharmaceutical category that leverages antibodies to facilitate drug delivery to target cells. A key challenge for ADCs is increasing the drug-antibody ratio (DAR) to improve efficacy without compromising their properties, such as pharmacokinetics. Here, we present a novel polypeptide-based platform that substantially increases the DAR of antibody-payload ADCs while minimally compromising the ADCs’ inherent characteristics. A polypeptide-based antibody-drug conjugate lead (polypeptide ADC 6c), capable of achieving a DAR of up to 61, was synthesized using the versatile click reaction method based on our polypeptide-based platform. 6c could efficiently recognize antigens, be subsequently endocytosed, and achieve subnanomolar activity at the cellular level. Moreover, 6c exhibited excellent pharmacokinetic parameters and potent antitumor efficacy in mice. Collectively, this study provides and characterizes a highly variable polypeptide backbone platform that can be used to efficiently develop innovative ADCs with high payloads for the treatment of various cancers
Ruyao Tang, Fusheng Guo, Jinyi Bai et al.· JACS Au· 0 citations
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