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1. Metabologenomics reveals strain-level genetic and chemical diversity of Microcystis secondary metabolism

   https://doi.org/10.1128/msystems.00334-24  

   Yancey, Colleen E; Hart, Lauren; Hefferan, Sierra; Mohamed, Osama G; Newmister, Sean A; Tripathi, Ashootosh; Sherman, David H; Dick, Gregory J (July 2024, mSystems)

   van_der_Hooft, Justin_J J (Ed.)

   ABSTRACT Microcystisspp. are renowned for producing the hepatotoxin microcystin in freshwater cyanobacterial harmful algal blooms around the world, threatening drinking water supplies and public and environmental health. However,Microcystisgenomes also harbor numerous biosynthetic gene clusters (BGCs) encoding the biosynthesis of other secondary metabolites, including many with toxic properties. Most of these BGCs are uncharacterized and currently lack links to biosynthesis products. However, recent field studies show that many of these BGCs are abundant and transcriptionally active in natural communities, suggesting potentially important yet unknown roles in bloom ecology and water quality. Here, we analyzed 21 xenicMicrocystiscultures isolated from western Lake Erie to investigate the diversity of the biosynthetic potential of this genus. Through metabologenomic andin silicoapproaches, we show that theseMicrocystisstrains contain variable BGCs, previously observed in natural populations, and encode distinct metabolomes across cultures. Additionally, we find that the majority of metabolites and gene clusters are uncharacterized, highlighting our limited understanding of the chemical repertoire ofMicrocystisspp. Due to the complex metabolomes observed in culture, which contain a wealth of diverse congeners as well as unknown metabolites, these results underscore the need to deeply explore and identify secondary metabolites produced byMicrocystisbeyond microcystins to assess their impacts on human and environmental health.IMPORTANCEThe genusMicrocystisforms dense cyanobacterial harmful algal blooms (cyanoHABs) and can produce the toxin microcystin, which has been responsible for drinking water crises around the world. While microcystins are of great concern,Microcystisalso produces an abundance of other secondary metabolites that may be of interest due to their potential for toxicity, ecological importance, or pharmaceutical applications. In this study, we combine genomic and metabolomic approaches to study the genes responsible for the biosynthesis of secondary metabolites as well as the chemical diversity of produced metabolites inMicrocystisstrains from the Western Lake Erie Culture Collection. This unique collection comprisesMicrocystisstrains that were directly isolated from western Lake Erie, which experiences substantial cyanoHAB events annually and has had negative impacts on drinking water, tourism, and industry. 

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2. New approaches to secondary metabolite discovery from anaerobic gut microbes

   https://doi.org/10.1007/s00253-024-13393-y  

   Butkovich, Lazarina_V; Vining, Oliver_B; O’Malley, Michelle_A (January 2025, Applied Microbiology and Biotechnology)

   AbstractThe animal gut microbiome is a complex system of diverse, predominantly anaerobic microbiota with secondary metabolite potential. These metabolites likely play roles in shaping microbial community membership and influencing animal host health. As such, novel secondary metabolites from gut microbes hold significant biotechnological and therapeutic interest. Despite their potential, gut microbes are largely untapped for secondary metabolites, with gut fungi and obligate anaerobes being particularly under-explored. To advance understanding of these metabolites, culture-based and (meta)genome-based approaches are essential. Culture-based approaches enable isolation, cultivation, and direct study of gut microbes, and (meta)genome-based approaches utilizeinsilicotools to mine biosynthetic gene clusters (BGCs) from microbes that have not yet been successfully cultured. In this mini-review, we highlight recent innovations in this area, including anaerobic biofoundries like ExFAB, the NSF BioFoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria. These facilities enable high-throughput workflows to study oxygen-sensitive microbes and biosynthetic machinery. Such recent advances promise to improve our understanding of the gut microbiome and its secondary metabolism. Key points• Gut microbial secondary metabolites have therapeutic and biotechnological potential• Culture- and (meta)genome-based workflows drive gut anaerobe metabolite discovery• Anaerobic biofoundries enable high-throughput workflows for metabolite discovery Graphical abstract 

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3. Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria

   https://doi.org/10.1038/s41598-020-58904-9  

   Belknap, Kaitlyn C.; Park, Cooper J.; Barth, Brian M.; Andam, Cheryl P. (February 2020, Scientific Reports)

   Abstract Streptomycesbacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the most prolific producer strains, knowledge about phylogenetic relationships ofStreptomycesspecies, genome-wide diversity and distribution patterns of BGCs is critical. We used genomic and phylogenetic methods to elucidate the diversity of major classes of BGCs in 1,110 publicly availableStreptomycesgenomes. Genome mining ofStreptomycesreveals high diversity of BGCs and variable distribution patterns in theStreptomycesphylogeny, even among very closely related strains. The most common BGCs are non-ribosomal peptide synthetases, type 1 polyketide synthases, terpenes, and lantipeptides. We also found that numerousStreptomycesspecies harbor BGCs known to encode antitumor compounds. We observed that strains that are considered the same species can vary tremendously in the BGCs they carry, suggesting that strain-level genome sequencing can uncover high levels of BGC diversity and potentially useful derivatives of any one compound. These findings suggest that a strain-level strategy for exploring secondary metabolites for clinical use provides an alternative or complementary approach to discovering novel pharmaceutical compounds from microbes. 

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4. Effects of phytoplankton, viral communities, and warming on free-living and particle-associated marine prokaryotic community structure

   https://doi.org/10.1038/s41467-022-35551-4  

   Yeh, Yi-Chun; Fuhrman, Jed A. (December 2022, Nature Communications)

   Abstract Free-living and particle-associated marine prokaryotes have physiological, genomic, and phylogenetic differences, yet factors influencing their temporal dynamics remain poorly constrained. In this study, we quantify the entire microbial community composition monthly over several years, including viruses, prokaryotes, phytoplankton, and total protists, from the San-Pedro Ocean Time-series using ribosomal RNA sequencing and viral metagenomics. Canonical analyses show that in addition to physicochemical factors, the double-stranded DNA viral community is the strongest factor predicting free-living prokaryotes, explaining 28% of variability, whereas the phytoplankton (via chloroplast 16S rRNA) community is strongest with particle-associated prokaryotes, explaining 31% of variability. Unexpectedly, protist community explains little variability. Our findings suggest that biotic interactions are significant determinants of the temporal dynamics of prokaryotes, and the relative importance of specific interactions varies depending on lifestyles. Also, warming influenced the prokaryotic community, which largely remained oligotrophic summer-like throughout 2014–15, with cyanobacterial populations shifting from cold-water ecotypes to warm-water ecotypes. 

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5. Quantitative microbial taxonomy across particle size, depth, and oxygen concentration

   https://doi.org/10.3389/fmicb.2025.1552305  

   Huanca-Valenzuela, Paulina; Fuchsman, Clara A; Tully, Benjamin J; Sylvan, Jason B; Cram, Jacob A (May 2025, Frontiers in Microbiology)

   Srivastava, Abhishek (Ed.)

   IntroductionMarine particles form in the ocean surface sink through the water column into the deep ocean, sequestering carbon. Microorganisms inhabit and consume carbon in these particles. The East Pacific Rise (EPR) harbors both an Oxygen Deficient Zone (ODZ) and a non-buoyant plume region formed from hydrothermal vents located on the ocean floor, allowing us to explore relationships between microbial community and particle size between a range of environments. MethodsIn this study, we quantified microbial diversity using a fractionation method that separated particles into seven fine scale fractions (0.2–1.2, 1.2–5, 5–20, 20–53, 53–180,180–500, >500 μm), and included a spike-in standard for sequencing the 16S rRNA gene. Size fractionated organic carbon into the same fractions enabled the calculation of bacterial 16S rRNA copies per μg C and per liter. ResultsThere was a large increase in the bacterial 16S rRNA copies/ug C and copies/L on particles >180 μm between the upper water column and the deep water column. Though the total concentration of organic C in particles decreased in the deep water column, the density of bacteria on large particles increased at depth. The microbial community varied statistically significantly as a function of particle size and depth. Quantitative abundance estimates found that ostensibly obligate free-living microbes, such as SAR11 and Thaumarcheota, were more abundant in the free-living fraction but also common and abundant in the particulate size fractions. Conversely, ostensibly obligate particle attached bacteria such as members of Bacteroidetes and Planctomycetes, while most abundant on particles, were also present in the free living fraction. Total bacterial abundance, and the abundance of many taxonomic groups, increased in the ODZ region, particularly in the free-living fraction. Contrastingly, in the non-buoyant plume, there were highly abundant bacteria in the 5–20 and 20–53 μm fractions but reduced bacteria present in the 53–180 and 180–500 μm fractions. ConclusionQuantitative examination of microbial communities highlights the distribution of microbial taxa unburdened by compositional effects. These data are congruent with existing models which suggest high levels of exchange between particle-attached and free-living communities. 

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