Summary
Natural products are small-molecule metabolites synthesised by plants, fungi, bacteria and marine organisms. They comprise diverse chemical classes—alkaloids, terpenoids, flavonoids, peptides and glycopeptides—often tailored by specialised biosynthetic enzymes. These compounds mediate ecological interactions in their native hosts and exert a broad spectrum of biological activities, including antimicrobial, anti-inflammatory, antioxidant and anticancer effects. Advances in genomics and enzymology have revealed the modular logic of nonribosomal peptide synthetase (NRPS) and polyketide synthase assembly lines, and the role of cytochrome P450 enzymes in forging rigid crosslinks in glycopeptide antibiotics. Concurrently, improvements in extraction techniques—from supercritical CO₂ to ultrasound and microwave-assisted methods—have enhanced yield and purity, while nanoformulation strategies protect labile structures and boost bioavailability. Natural scaffolds continue to inspire drug discovery, probe enzyme mechanisms and underpin sustainable agrochemical and nutraceutical development.
Research from Nature Portfolio
Studies on kistamicin biosynthesis have demonstrated how two P450 “Oxy” enzymes, in concert with a unique NRPS X-domain, install three aromatic crosslinks—including an unusual A–O–B macrocycle—on a heptapeptide precursor. Structural and functional analyses reveal that one Oxy enzyme displays remarkable promiscuity, while the sequential order of cyclisation is dictated by precise X-domain docking, clarifying a longstanding puzzle in glycopeptide assembly. In parallel, in vitro reconstitution of teicoplanin cyclisation has provided the first biochemical characterisation of the OxyE enzyme. OxyE is shown to require prior installation of a C–O–D ring by OxyB and direct interaction with the X-domain to form the F–O–G ring, uncovering how subtle stereochemical and docking interfaces govern tricyclic aglycone formation.
Research from all publishers
Investigations into the traditional herb Centipeda minima have yielded new plant-derived anticancer leads. The crude extract suppresses proliferation and induces apoptosis in triple-negative breast cancer models by concurrently inhibiting receptor tyrosine kinases and survival cascades—including EGFR, PI3K/AKT/mTOR, NF-κB and STAT3—and by downregulating matrix metalloproteinases. Isolation of sesquiterpene lactones such as Brevilin A and Arnicolide D revealed their ability to trigger G₂/M arrest, activate caspases and modulate cyclin and Bcl-2 family proteins. In xenograft studies, these compounds achieved tumour regression comparable to standard chemotherapeutics with minimal toxicity to healthy tissue. Meanwhile, sesterterpenoids—25-carbon isoprenoids from marine fungi and plants—have emerged as potent cytotoxins at low micromolar concentrations. Structure–activity relationship analyses highlight that oxacyclic and epoxide moieties enhance cellular uptake and target engagement. Biosynthetic studies of geranylfarnesyl diphosphate cyclisation have uncovered sequential carbocation rearrangements, offering routes to engineer new analogues with improved pharmacokinetic profiles.
Natural Products and Bioactive Compounds publication trend
The graph below shows the total number of articles in natural products and bioactive compounds across all publications each year (not limited to Nature Index journals).
Technical terms
Nonribosomal peptide synthetase (NRPS): A modular enzyme complex that assembles peptide chains independently of the ribosome, using adenylation, thiolation and condensation domains.
Cytochrome P450 Oxy enzyme: A haem-containing monooxygenase that catalyses oxidative phenol coupling to create crosslinks in glycopeptide antibiotic precursors.
X-domain: A specialised docking module within NRPS that recruits P450 enzymes for site-specific cyclisation of peptide substrates.
Apoptosis: Programmed cell death mediated by caspase activation, DNA fragmentation and membrane blebbing.
PI3K/AKT/mTOR pathway: A central signalling network regulating cell growth, proliferation and survival, often hyperactivated in cancer.
Sesterterpenoid: A terpenoid composed of five isoprene units (25 carbons) featuring complex polycyclic scaffolds and diverse biological activities.
References
- Kistamicin biosynthesis reveals the biosynthetic requirements for production of highly crosslinked glycopeptide antibiotics. Nature Communications (2019).
- F-O-G Ring Formation in Glycopeptide Antibiotic Biosynthesis is Catalysed by OxyE. Scientific Reports (2016).
- Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways. Frontiers in Oncology (2020).
- Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma. Molecules (2019).
- Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma. Frontiers in Pharmacology (2019).
- Targeting cancer with sesterterpenoids: the new potential antitumor drugs. Journal of Natural Medicines (2015).
- Biosynthetic insights provided by unusual sesterterpenes from the medicinal herb Aletris farinosa. Chemical Science (2015).
- Introduction.
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