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natural products

  • Open Access
    Cryptic or Silent? The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism
    Perspective | Applied and Environmental Science
    Cryptic or Silent? The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism

    Microbial natural products, particularly those produced by filamentous Actinobacteria, underpin the majority of clinically used antibiotics. Unfortunately, only a few new antibiotic classes have been discovered since the 1970s, which has exacerbated fears of a postapocalyptic world in which antibiotics have lost their utility. Excitingly, the genome sequencing revolution painted an entirely new picture, one in which an average...

    Paul A. Hoskisson, Ryan F. Seipke
  • Open Access
    Heterologous Expression of the Unusual Terreazepine Biosynthetic Gene Cluster Reveals a Promising Approach for Identifying New Chemical Scaffolds
    Editor's Pick Research Article | Applied and Environmental Science
    Heterologous Expression of the Unusual Terreazepine Biosynthetic Gene Cluster Reveals a Promising Approach for Identifying New Chemical Scaffolds

    Here, we provide evidence that Aspergillus terreus encodes a biosynthetic gene cluster containing a repurposed indoleamine 2,3-dioxygenase (IDO) dedicated to secondary metabolite synthesis. The discovery of this neofunctionalized IDO not only enabled discovery of a new compound with an unusual chemical scaffold but also provided insight into the numerous strategies...

    Lindsay K. Caesar, Matthew T. Robey, Michael Swyers, Md N. Islam, Rosa Ye, Purav P. Vagadia, Gary E. Schiltz, Paul M. Thomas, Chengcang C. Wu, Neil L. Kelleher, Nancy P. Keller, Jin Woo Bok
  • Open Access
    An Antivirulence Approach for Preventing <span class="named-content genus-species" id="named-content-1">Cryptococcus neoformans</span> from Crossing the Blood-Brain Barrier via Novel Natural Product Inhibitors of a Fungal Metalloprotease
    Research Article | Therapeutics and Prevention
    An Antivirulence Approach for Preventing Cryptococcus neoformans from Crossing the Blood-Brain Barrier via Novel Natural Product Inhibitors of a Fungal Metalloprotease

    Fungal infections like cryptococcal meningitis are difficult to resolve because of the limited therapies available. The small arsenal of antifungal drugs reflect the difficulty in finding available targets in fungi because like mammalian cells, fungi are eukaryotes. The limited efficacy, toxicity, and rising resistance of antifungals contribute to the high morbidity and mortality of fungal infections and further underscore the dire but...

    Phylicia A. Aaron, Kiem Vu, Angie Gelli
  • Open Access
    Multi-Omic Analyses Provide Links between Low-Dose Antibiotic Treatment and Induction of Secondary Metabolism in <span class="named-content genus-species" id="named-content-1">Burkholderia thailandensis</span>
    Research Article | Molecular Biology and Physiology
    Multi-Omic Analyses Provide Links between Low-Dose Antibiotic Treatment and Induction of Secondary Metabolism in Burkholderia thailandensis

    The discovery of antibiotics ranks among the most significant accomplishments of the last century. Although the targets of nearly all clinical antibiotics are known, our understanding regarding their natural functions and the effects of subinhibitory concentrations is in its infancy. Stimulatory rather than inhibitory functions have been attributed to low-dose antibiotics. Among these, we previously found that antibiotics activate...

    Anran Li, Dainan Mao, Aya Yoshimura, Paul C. Rosen, W. Lance Martin, Étienne Gallant, Martin Wühr, Mohammad R. Seyedsayamdost
  • Open Access
    Horizontal Gene Transfer to a Defensive Symbiont with a Reduced Genome in a Multipartite Beetle Microbiome
    Editor's Pick Research Article | Host-Microbe Biology
    Horizontal Gene Transfer to a Defensive Symbiont with a Reduced Genome in a Multipartite Beetle Microbiome

    Associations between microorganisms and an animal, plant, or fungal host can result in increased dependence over time. This process is due partly to the bacterium not needing to produce nutrients that the host provides, leading to loss of genes that it would need to live independently and to a consequent reduction in genome size. It is often thought that genome reduction is aided by genetic isolation—bacteria that live in monocultures...

    Samantha C. Waterworth, Laura V. Flórez, Evan R. Rees, Christian Hertweck, Martin Kaltenpoth, Jason C. Kwan
  • Open Access
    Comparative Genomics of Cyanobacterial Symbionts Reveals Distinct, Specialized Metabolism in Tropical <em>Dysideidae</em> Sponges
    Research Article | Applied and Environmental Science
    Comparative Genomics of Cyanobacterial Symbionts Reveals Distinct, Specialized Metabolism in Tropical Dysideidae Sponges

    Natural products provide the inspiration for most clinical drugs. With the rise in antibiotic resistance, it is imperative to discover new sources of chemical diversity. Bacteria living in symbiosis with marine invertebrates have emerged as an untapped source of natural chemistry. While symbiotic bacteria are often recalcitrant to growth in the lab, advances in metagenomic sequencing and assembly now make it possible to access their...

    Michelle A. Schorn, Peter A. Jordan, Sheila Podell, Jessica M. Blanton, Vinayak Agarwal, Jason S. Biggs, Eric E. Allen, Bradley S. Moore
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