Cinnamosyn, a Cinnamoylated Synthetic-Bioinformatic Natural Product with Cytotoxic Activity.

Most biosynthetic gene clusters (BGCs) are functionally inaccessible by using fermentation methods. Bioinformatic-coupled total synthesis provides an alternative approach for accessing BGC-encoded bioactivities. To date, synthetic bioinformatic natural product (synBNP) methods have focused on lipopeptides containing simple lipids.

Multiplexed mobilization and expression of biosynthetic gene clusters.

Bacterial genomes contain large reservoirs of biosynthetic gene clusters (BGCs) that are predicted to encode unexplored natural products. Heterologous expression of previously unstudied BGCs should facilitate the discovery of additional therapeutically relevant bioactive molecules from bacterial culture collections, but the large-scale manipulation of BGCs remains cumbersome. Here, we describe a method to parallelize the identification, mobilization and heterologous expression of BGCs.

Identification of structurally diverse menaquinone-binding antibiotics with in vivo activity against multidrug-resistant pathogens.

The emergence of multidrug-resistant bacteria poses a threat to global health and necessitates the development of additional in vivo active antibiotics with diverse modes of action. Directly targeting menaquinone (MK), which plays an important role in bacterial electron transport, is an appealing, yet underexplored, mode of action due to a dearth of MK-binding molecules. Here we combine sequence-based metagenomic mining with a motif search of bioinformatically predicted natural product structures to identify six biosynthetic gene clusters that we predicted encode MK-binding antibiotics (MBAs).

Biosynthetic Interrogation of Soil Metagenomes Reveals Metamarin, an Uncommon Cyclomarin Congener with Activity against .

Tuberculosis (TB) remains one of the deadliest infectious diseases. Unfortunately, the development of antibiotic resistance threatens our current therapeutic arsenal, which has necessitated the discovery and development of novel antibiotics against drug-resistant (). Cyclomarin A and rufomycin I are structurally related cyclic heptapeptides assembled by nonribosomal peptide synthetases (NRPSs), which show potent anti- activity with a new cellular target, the caseinolytic protein ClpC1.

An Ichip-Domesticated Sponge Bacterium Produces an -Acyltyrosine Bearing an α-Methyl Substituent.

The ichip (isolation chip) was employed for the first time in a marine sponge (), and a putatively new bacterial species, sp. RKMC-009, was isolated. Strain RKMC-009 produces a novel -acyltyrosine () that is appended with a rare α-methyl substituent within the aminoacyl moiety and also exhibits Gram-positive antibacterial activity.

Draft Genome Sequence of sp. Strain RKMC-009, Isolated from via Culturing Using an Isolation Chip Diffusion Chamber.

We report the draft whole-genome sequence of sp. strain RKMC-009, which was isolated from the sponge in San Salvador, The Bahamas, using an isolation chip (ichip). Automated biosynthetic gene cluster analysis using antiSMASH 4.

Fusaristatin C, a Cyclic Lipodepsipeptide from Pithomyces sp. RKDO 1698.

A new cyclic lipodepsipeptide, fusaristatin C (1), was obtained from the fungus Pithomyces sp. RKDO 1698, which was isolated from the Caribbean octocoral Eunicea fusca. The 2D structure of fusaristatin C was elucidated using NMR spectroscopy and mass spectrometry, while the absolute configuration of the sole chiral amino acid residue (l-serine) was determined using Marfey's method.

Isolation of Imaqobactin, an Amphiphilic Siderophore from the Arctic Marine Bacterium Variovorax Species RKJM285.

The amphiphilic siderophore imaqobactin was isolated from the Arctic bacterium Variovorax sp. RKJM285, a strain isolated from marine sediment collected from an inlet near Clyde River, Nunavut, Canada. The 2D structure of imaqobactin was determined by a combination of LC-HRMS, MS/MS, and NMR spectroscopic methods.

Post Polyketide Synthase Carbon-Carbon Bond Formation in Type-II PKS-Derived Natural Products from Streptomyces venezuelae.

Polyketide synthase (PKS) derived natural products are biosynthesized by head-to-tail addition of acetate and malonate extender units resulting in linear extended-polyketide chains. Despite the well-documented structural diversity associated with PKS-derived natural products, C-C chain branching deviating from the usual linear pattern is relatively rare. Herein, type-II PKS angucyclic natural products containing a hemiaminal functionality were identified and proposed as the parent of a series of C-C-branched analogues.