Four new polyketides, heterocornol Y (1), stemphyindan (2), pestalospirane C (3), and stemphyspyrane (4), along with five known ones (5–9) were isolated from the endophytic fungus Stemphylium globuliferum 17035 (SG17035) based on the One Strain Many Compounds (OSMAC) strategy allied with an LC-MS approach. These structures were elucidated through extensive spectroscopic analyses, single-crystal X-ray diffraction, and ¹³C NMR-DP4 analysis. Pestalospirane C (3) and stemphyspyrane (4) featured unprecedented spiroketal skeletons. In addition, the putative biosynthetic logic for compounds 1–4 was proposed. Antibacterial and cytotoxic activities of compounds 1–9 were evaluated. Stemphyspyrane (4) displayed promising antibacterial activity against different pathogens, especially against Staphylococcus aureus, Porphyromonas gingivalis, and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 3.125 μM, 6.25 μM, and 12.5 μM, respectively. It is promising as an antibacterial agent for further optimization.

Phytopathogenic fungi have attracted great attention as a promising source for new drug discovery. In the progress of our ongoing study for bioactive natural products from an in-house phytopathogenic fungi library, a pathogenic fungus, Fusarium proliferatum strain 13294 (FP13294), was selected for chemical investigation. Two novel aliphatic unsaturated alcohols named fusariumnols A and B (1 and 2), together with one previously characterized sesquiterpenoid lignoren (3) were identified. Structures of 1–3 were assigned by mass spectrometry and NMR spectroscopy. Their bioactivities were assessed against Staphylococcus epidermidis, S. aureus, and Methicillin-resistant S. aureus (MRSA). Compounds 1 and 2 exhibited weak antibacterial activity against S. epidermidis (MIC = 100 μM).

Sesquiterpenoids represent a structurally diverse class of natural products widely recognized for their ecological significance and pharmacological potential, including antimicrobial, anti-inflammatory, and anticancer properties. As part of our efforts to explore bioactive secondary metabolites from phytopathogenic fungi, we conducted a molecular networking-based analysis of Bipolaris sorokiniana isolate BS11134, which was fermented on a rice medium. This analysis led to the identification of three new seco-sativene-type sesquiterpenoids (1–3) and seven known analogues (4–10), with the NMR data of compound 4 being reported for the first time. The structures of these compounds were elucidated using HR-ESI-MS and extensive spectroscopic data analysis. Notably, compound 9 significantly inhibited nitrous oxide expression in lipopolysaccharide (LPS)-treated RAW264.7 cells in vitro (inhibition rate: 84.7 ± 1.7% at 10 μM), while compound 1 (10 μM) showed a weak inhibitory effect (inhibition rate = 28.0 ± 2.4%). Additionally, we proposed a biosynthetic pathway for these compounds. This study not only expands the chemical space of the helminthoporene class of molecules but also underscores the untapped potential of phytopathogenic fungi as promising sources of structurally unique and biologically active natural products. Graphical Abstract

Phosphonate natural products, characterized by a stable carbon–phosphorus (C–P) bond, represent a distinctive class of natural products with broad bioactivities and diverse applications in medicine and agriculture. Despite their potential, the field has lacked a systematic, quantitatively informed synthesis linking discovery trends to biological function and scalable production. In this review, we curate 71 reports of phosphonate natural products between 1959 and the present, primarily from bacterial sources, and analyze them across discovery modalities, bioactivity profiles, and producer taxonomy. We further summarize structure–activity relationships and consolidate engineering strategies—including metabolic engineering, synthetic biology, and biocatalytic cascades—employed to enhance phosphonate yields. Based on these analyses, we propose practical directions to accelerate the discovery of novel phosphonates, and improve their accessibility through advances in production and isolation technologies.

Streptomyces species continue to occupy a pivotal role in natural product biosynthesis, owing to their unparalleled metabolic diversity and genetic adaptability. This review focuses on cutting-edge advances documented from 2020 to 2025 (encompassing approximately 150 cases), with particular emphasis on innovations in canonical/non-canonical Streptomyces chassis engineering. We synthesize key developments across genome streamlining, mitigation of endogenous interference, redistribution of precursors and cofactors, regulatory circuit reprogramming, optimization of phylogenetic host-cluster compatibility, and enhancement of fermentation robustness. These strategies collectively transform Streptomyces into versatile, application-specific production platforms. A standout innovation highlighted herein is the 5M strategy (Mechanism–Model–Manipulate–Measure–Manufacture), which reframes chassis engineering as an iterative, systems-level process inspired by engineering principles. This framework fosters precise manipulation and strain-bioreactor synergy, based on a deep comprehension of metabolic mechanisms and bioreactor compatibility dynamics, thereby facilitating scalable manufacturing of high-value compounds. By providing a structured roadmap, this perspective equips researchers with actionable insights for advancing next-generation Streptomyces chassis in synthetic biology and industrial biotechnology. Furthermore, we explore emerging technological breakthroughs, such as AI-driven design tools, multiplexed genome editing technologies, and hybrid chemical-enzymatic integration strategies, that are poised to accelerate the evolution toward intelligent, modular chassis architectures. Ultimately, this review offers a practical resource for advancing Streptomyces applications in natural product discovery, functional characterization, and yield enhancement, supporting incremental improvements in biotechnological applications.