Novel natural products (NPs) and their derivatives are important sources for drug discovery, which have been broadly applied in the fields of agriculture, livestock, and medicine, making the synthesis of NPs and their derivatives necessarily important. In recent years, biosynthesis technology has received increasing attention due to its high efficiency in the synthesis of high value-added novel products and its advantages of green, environmental protection, and controllability. In this review, the technological advances of biosynthesis strategies in the discovery of novel NPs and their derivatives are outlined, with an emphasis on two areas of host engineering and enzymatic synthesis. In terms of hosts engineering, multiple microorganisms, including , , and , have been used as the biosynthetic gene clusters (BGCs) provider and host strain for the expression of BGCs to discover new compounds over the past years. In addition, the use of enzymatic synthesis strategy to generate novel compounds such as triterpenoid saponins and flavonoids is also hereby described.
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http://dx.doi.org/10.1080/07388551.2023.2236787 | DOI Listing |
Commun Biol
January 2025
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
P4-ATPases, a subfamily of the P-type ATPase superfamily, play a crucial role in translocating membrane lipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet. This process generates and regulates transbilayer lipid asymmetry. These enzymes are conserved across all eukaryotes, and the human genome encodes 14 distinct P4-ATPases.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens.
View Article and Find Full Text PDFPlant Physiol
December 2024
Department of Biology, University of Oxford, South Parks Road, Oxford OX1 3RB, UK.
The cysteine/arginine (Cys/Arg) branch of the N-degron pathway controls the stability of certain proteins with methionine (Met)-Cys N-termini, initiated by Met cleavage and Cys oxidation. In seeding plants, target proteins include the Group VII Ethylene Response Factors, which initiate adaptive responses to low oxygen (hypoxic) stress, as well as Vernalization 2 (VRN2) and Little Zipper 2 (ZPR2), which are involved in responses to endogenous developmental hypoxia. It is essential that these target proteins are only degraded by the N-degron pathway under the appropriate physiological conditions.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801.
Enzyme-enzyme interactions are fundamental to the function of cells. Their atomistic mechanisms remain elusive mainly due to limitations of in-cell measurements. We address this challenge by atomistically modeling, for a total of ≈80 μs, a slice of the human cell cytoplasm that includes three successive enzymes along the glycolytic pathway: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), and phosphoglycerate mutase (PGM).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Republic of Korea.
The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146 in the active state has been well studied, the role of the reduced cysteine residues, Cys6 and Cys111, in SOD1 filament formation remains unclear. In this study, we investigated the role of reduced cysteine residues by determining and comparing cryoelectron microscopy (cryo-EM) structures of wild-type (WT) and C6A/C111A SOD1 filaments under thiol-based reducing and metal-depriving conditions, starting with protein samples possessing enzymatic activity.
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