Labilomycin

Menaquinone is an essential cofactor in the electron-transfer pathway for bacteria. Menaquinone is biosynthesized from chorismate using either the well-known canonical pathway established by pioneering studies in model microorganisms or the futalosine pathway, which we discovered in Streptomyces. Because Helicobacter pylori, which causes stomach cancer, uses the futalosine pathway and most beneficial intestinal bacteria including lactobacilli use the canonical pathway, the futalosine pathway will be a great target to develop antibiotics specific for H. pylori. Here, we searched for such compounds from metabolites produced by actinomycetes and identified pulvomycin from culture broth of Streptomyces sp. K18-0194 as a specific inhibitor of the futalosine pathway.

A synthetic route to the pulvomycin class of natural products is presented, which culminated in the first synthesis of a pulvomycin, pulvomycin D. Key elements of the strategy include a pivotal aldol reaction which led to bond formation between the C24-C40 and the C8-C23 fragment. The remaining C1-C7 fragment was attached by a Yamaguchi esterification completing the assembly of the 40 carbon atoms within the main skeleton. Ring closure to the 22-membered lactone ring was achieved in the final stages of the synthesis by a Heck reaction. The completion of the synthesis required the removal of six silyl protecting groups in combination with olefin formation at C26-C27 by a Peterson elimination.

To understand antibiotic resistance in pathogenic bacteria, we need to monitor environmental microbes as reservoirs of antimicrobial resistance genes (ARGs). These bacteria are present in the air and can be investigated with the whole metagenome shotgun sequencing approach. This study aimed to investigate the feasibility of a method for metagenomic analysis of microbial composition and ARGs in the outdoor air. Air samples were collected with a Harvard impactor in the PM10 range at 50 m from a hospital in Budapest. From the DNA yielded from samples of PM10 fraction single-end reads were generated with an Ion Torrent sequencer. During the metagenomic analysis, reads were classified taxonomically. The core bacteriome was defined. Reads were assembled to contigs and the ARG content was analyzed. The dominant genera in the core bacteriome were Bacillus, Acinetobacter, Leclercia and Paenibacillus. Among the identified ARGs best hits were vanRA, Bla1, mphL, Escherichia coli EF-Tu mutants conferring resistance to pulvomycin; BcI, FosB, and mphM. Despite the low DNA content of the samples of PM10 fraction, the number of detected airborne ARGs was surprisingly high.