📢 Our new open-access review, “Extracting Value from Marine and Microbial Natural Product Artifacts and Chemical Reactivity,” is now published in Marine Drugs.

Together with Rob Capon, we explore how chemically reactive natural products—and the artifacts they generate—are far more than analytical nuisances. When properly recognised and understood, these transformations can expose untapped regions of chemical space and create new opportunities for drug discovery and marine bioproduct development.

🔎 What is covered:

• Why artifact formation matters in natural product chemistry.
• The mechanisms (solvents, heat, pH, light, oxidation) that trigger transformations.
• Case studies showing how artifacts can provide novel insight and value including how identify “cryptic” natural products.
• Practical recommendations for recognising, controlling, and leveraging chemical reactivity in natural products research.

💡 One particularly instructive example of chemical instability is varacin (2.66, see figure), a benzopentathiepin with cytotoxic activity first reported from a Fijian ascidian Lissoclinum vareau in 1991. This striking and unusual structure attracted considerable attention at the time! A subsequent study reported varacin together with three closely related analogues, varacins A–C (2.67–2.69), from a Polycitor sp. ascidian. Notably, varacin and varacin A were shown to equilibrate with elemental sulfur (S₈, 2.70) in solution (MeOH, CH₂Cl₂, or pyridine), underscoring their chemical lability.

Related sulfur-rich systems are known to undergo light-induced sulfur radical formation, leading to sulfur ring expansion and contraction via desulfurisation and intermolecular disproportionation (see the review for further examples such as the chetomins and epithiodiketopiperazines). In the case of varacin, recombination of sulfur radicals lead to the formation of the most thermodynamically stable sulfur allotrope, S₈, in equilibrium with varacin and varacin A.

#NaturalProducts #MarineDrugs #DrugDiscovery #Chemistry #ChemicalBiology #MarineBioproducts #Research

⚠️ Nature-inspired antibiotics have been the foundation of modern medicine for over a century, but their effectiveness is under threat from drug resistance.

❓How many nature-inspired antibiotics have been approved for human use? What are their structures? Who developed and launched them, in what countries, when and for what infectious diseases? How do they work and are they still being used today?

⏳In a review publish today in Natural Product Reports, co-authored with Rob Capon, we answer all these questions and more, providing details and charting trends from the first approval of penicillin G in 1943 to 2025, backed up by over 1,000 literature citations.

👀 Some eye-opening facts:

• 217 natural product-inspired antibiotics have been used to treat human bacterial infections since 1943.
• Around 151 are still in use with around 24 only in limited use.
• 122 (81%) belong to just 5 classes: beta-lactams (71, 46%), macrolides (15, 9.9%), aminoglycosides (14, 9.3%), tetracyclines (12, 7.9%) and peptides (10, 6.6%).
• Only 3 new natural product drug classes have been approved since 2000 (daptomycin, pleuromutilin and fidaxomicin)

⏰The clock is ticking…. to learn more, follow the link.

#Antibiotics #DrugDiscovery #NatureInspired #AMR #PharmaResearch #InfectiousDiseases #NaturalProducts #MedicalResearch #GlobalHealth #ScienceCommunication

AMR is continuing to spread, but so are new models for access. Cefiderocol shows what the future of equitable antibiotics could look like.

As antimicrobial resistance continues to accelerate, particularly among carbapenem-resistant Gram-negative bacteria, cefiderocol has emerged as one of the most important new antibiotics of the past decade. Developed by Shionogi, cefiderocol is a siderophore-conjugated cephalosporin that exploits bacterial iron-uptake systems to reach the periplasm and inhibit penicillin-binding proteins. Equally important is the way it is becoming increasingly available worldwide.

🌍 While cefiderocol is currently available in Japan, the USA, the EU, and Taiwan, Shionogi’s partnership with GARDP and Orchid Pharma will reshape what equitable antibiotic access can look like.

🤝 In short, GARDP holds the licence to supply cefiderocol across 135 countries, including most low- and middle-income nations. Orchid Pharma (India) will manufacture an affordable generic version via technology transfer and a cost-plus pricing model. The goal: ensure that countries carrying the highest AMR burden aren’t the last to receive new antibiotics. More information: GARDP video and Shionogi’s website.

💊 What’s happening in Australia? An NDA for cefiderocol was accepted by the TGA in December 2024 and remains under evaluation. In April 2025, Shionogi announced an exclusive licensing agreement with Link Healthcare for development and commercialisation in Australia and New Zealand. In the interim, cefiderocol is accessible via the TGA Special Access Scheme (SAS), with 49 requests in 2023 (see 30 July FOI disclosure).

🌟 Why This Matters…

◆ Cefiderocol’s story isn’t just about a new antibiotic. It’s about building sustainable, equitable pathways to ensure life-saving AMR tools reach every region that needs them—not only high-income markets. ✔️

◆ Innovative access models like this could become the blueprint for future global preparedness against AMR. 🎯

I am pleased to announce that we (Mark S. Butler, Ian R. Henderson, Robert J. Capon and Mark A. T. Blaskovich) have been awarded the 2024 Journal of Antibiotics Ōmura Award for Reviews’ Medal for the review “Antibiotics in the clinical pipeline as of December 2022”.

It is an honour to receive an award named after Prof. Satoshi Ōmura, the 2015 Nobel Laureate and Japanese microbiologist renowned for his discovery of avermectins, which led to the development of ivermectin—a breakthrough that has transformed global health by combating parasitic diseases such as river blindness and lymphatic filariasis. His pioneering work at Kitasato University, Tokyo, exemplifies the power of natural product research in saving millions of lives.

Flightpath Biosciences has begun human clinical testing for FP-100 (hygromycin A), which has potent activity against several spirochete Gram-negative bacteria such as Borrelia burgdorferi (Lyme disease) and Treponema pallidum (syphilis). Other spirochete-driven diseases include yaws (T. pallidum pertenue), advanced periodontal disease (T. denticola), and leptospirosis (Leptospira spp.). Spirochete bacteria have non-standard outer membranes compared with typical Gram-negative bacteria. These consist of an outer phospholipid bilayer (enriched in phosphatidylcholine and phosphatidylglycerol, lacking lipopolysaccharide (LPS)) with abundant lipoproteins such as OspA and OspC.

Hygromycin A was first discovered in the 1950s but overlooked due to the era’s focus on broad-spectrum antibiotics. Hygromycin A inhibits bacterial protein synthesis via ribosomal 23S rRNA binding and its structure is not currently represented in approved antibiotics. Several research programs have investigated hygromycin A analogues, including a Pfizer program that reported a more potent analogue CE-156811 in 2011, but none have made it clinical trials.

Using bioassay guided isolation to identify compounds with selective activity against B. burgdorferi over Staphylococcus aureus, Kim Lewis’s team at Northeastern University rediscovered hygromycin A (published in Cell in 2021). Promisingly, it showed in vitro and in vivo activity against B. burgdorferi. In addition, hygromycin A does not disrupt the growth of beneficial gut bacteria, unlike current treatments such as doxycycline. It was also shown that hygromycin A enters the bacterium via a nucleoside transporter, which is not present in most other bacteria. Flightpath Biosciences licensed hygromycin A in 2021 and a phase I trial (ACTRN12623001153606) was completed in March 2025 (results pending).

In North America and Europe, Lyme disease is caused by the B. burgdorferi sensu lato complex (including B. burgdorferi sensu stricto, B. afzelii, and B. garinii), transmitted by Ixodes ticks. Diagnosis is based on characteristic symptoms, history of exposure, and serology/PCR. Lyme disease affects an estimated 476,000 people annually in the U.S. alone, with up to 20% of patients experiencing persistent symptoms due to treatment limitations. However, in other countries such as Australia, where B. burgdorferi is not endemic, there is debate about what causes “Lyme-like illness”. Some Australians who have not travelled internationally develop chronic, multi-system illnesses after tick bites, but the cause is uncertain.

In conclusion, with its B. burgdorferi (spirochete) and microbiome-sparing selectivity, hygromycin A (FP-100) represents a promising advance in the treatment of Lyme disease. Its development highlights the value of continually revisiting natural products to address persistent global health challenges.

#LymeDisease #Antibiotics #Antibacterial #AntibioticInnovation #Biotech #InfectiousDisease #NaturalProducts #Actinomycetes #Bacteria