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Our understanding of secondary metabolite production in bacteria has been shaped primarily by studies of attached varieties such as symbionts, pathogens, and soil bacteria. Here we show that a strain of the single-celled, planktonic marine cyanobacterium Prochlorococcus--which conducts a sizable fraction of photosynthesis in the oceans--produces many cyclic, lanthionine-containing peptides (lantipeptides). Remarkably, in Prochlorococcus MIT9313 a single promiscuous enzyme transforms up to 29 different linear ribosomally synthesized peptides into a library of polycyclic, conformationally constrained products with highly diverse ring topologies. Genes encoding this system are found in variable abundances across the oceans--with a hot spot in a Galapagos hypersaline lagoon--suggesting they play a habitat-and/or community-specific role. The extraordinarily efficient pathway for generating structural diversity enables these cyanobacteria to produce as many secondary metabolites as model antibiotic-producing bacteria, but with much smaller genomes. lantibiotic | Synechococcus | combinatorial biosynthesis | Global Ocean Survey rnetagenorne doi/ 10.1073/pnas.0913677107

Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8-/-) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8-/- ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-α. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-κB activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma. [ABSTRACT FROM AUTHOR]

Our understanding of secondary metabolite production in bacteria has been shaped primarily by studies of attached varieties such as symbionts, pathogens, and soil bacteria. Here we show that a strain of the single-celled. planktonic marine canobacterium Pro- ch!orococcus-which conducts a sizable fraction of photosynthesis in the oceans-produces many cyclic, lanthionine-containing peptides (lantipeptides). Remarkably, in Proch!orococcus M1T931 3 a single promiscuous enzyme transforms up to 29 different linear ribosomally synthesized peptides into a library of polycyclic, conformationally constrained products with highly diverse ring topologies. Genes encoding this system are found in variable abun- dances across the oceans-with a hot spot in a Galapagos hypersa- line lagoon-suggesting they play a habitat- and/or community- specific role. The extraordinarily efficient pathway for generating structural diversity enables these cyanobacteria to produce as many secondary metabolites as model antibiotic-producing bacter- ia, but with much smaller genomes. [ABSTRACT FROM AUTHOR]

The article presents a study which explores the combination of physiology, enzymology, and sequencing approaches addressing the strategy used by cyanophages in phage replication. It notes that studies made on genomes have revealed the widespread presence of auxiliary metabolic genes that contain encodings similar to those used in host metabolism. Moreover, a simple model of host metabolism is illustrated that explains the relation between host cyanobacterial metabolism and phage infection.

Community composition within the human microbiome varies across individuals, but it remains unknown if this variation is sufficient to uniquely identify individuals within large populations or stable enough to identify them over time. We investigated this by developing a hitting set-based coding algorithm and applying it to the Human Microbiome Project population. Our approach defined body site-specific metagenomic codes: sets of microbial taxa or genes prioritized to uniquely and stably identify individuals. Codes capturing strain variation in clade-specific marker genes were able to distinguish among 100s of individuals at an initial sampling time point. In comparisons with follow-up samples collected 30-300 d later, ∼30% of individuals could still be uniquely pinpointed using metagenomic codes from a typical body site; coincidental (false positive) matches were rare. Codes based on the gut microbiome were exceptionally stable and pinpointed >80% of individuals. The failure of a code to match its owner at a later time point was largely explained by the loss of specific microbial strains (at current limits of detection) and was only weakly associated with the length of the sampling interval. In addition to highlighting patterns of temporal variation in the ecology of the human microbiome, this work demonstrates the feasibility of microbiome-based identifiability-a result with important ethical implications for microbiome study design. The datasets and code used in this work are available for download from huttenhower.sph.harvard.edu/idability.