Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 are producers of the antibiotic nucleocidin and 4′-fluoroadenosine is identified as a co-product

Abstract

Genome homologies led to the identification of Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 as producers of the antibiotic nucleocidin, and also 4’-fluoroadenosine.

Identification of Genes Essential for Sulfamate and Fluorine Incorporation During Nucleocidin Biosynthesis

“…A distinct clade is formed by S. calvus ATCC 13382, S. calvus NR_041122, S. virens NR_043842, S. asterosporus NR_041193, and S. aureorectus NR_041195, with the 16S rRNA sequences having 99 % or greater identity. An analogous phylogenetic relationship was reported by Chen and co‐workers [34] . Whole genome sequencing followed by AntiSMASH analysis revealed that S. virens and S. aureorectus contain 35 and 37 predicted BGCs, respectively (Tables S1, S2).…”

“… [18] The S. virens and S. aureorectus samples revealed 19 F{ 1 H} NMR signals consistent with the known fluoronucleosides 1 (δ=−121.0 ppm), 5 (−119.2 ppm), and 6 (−121.5 ppm). Chen and co‐workers observed production of these compounds along with low levels of 4 in S. virens [34] …”

“…While this manuscript was in preparation, Chen and co-workers used an identical approach to identify these same strains as producers of 1 and related fluoronucleosides. [34] We show that while these strains are closely related to S. calvus, they are more than 30times better producers of fluoronucleosides, and therefore serve as ideal strains for biosynthetic studies. We performed gene disruption experiments on S. virens within the BGC encoding 1, revealing for the first-time genes that differentially affect sulfamate and total fluoronucleoside biosynthesis.…”

“…This includes essentially identical BGCs (95 % to 100 % identity) that encode the non‐ribosomal peptide WS9326a, the polyketide annimycin, and 1 , all of which are characteristic metabolites produced by S. calvus and S. asterosporus [35–37] . Chen and co‐workers reported that the BGC for 1 in S. virens was missing several genes relative to S. calvus , including orf181 , nucM , and nucG [34] . However, this observation is likely based on an error in genome sequencing or assembly, as we observe 99.4 % DNA sequence identity between the BGCs for 1 in S. virens , S. aureorectus relative to S. calvus (Figure S2).…”

“…In this study we have extended the use of 16S rRNA sequence homology to identify Streptomyces virens NRRL B‐24331 and Streptomyces aureorectus NRRL B‐24301 as new producers of 1 and related fluoronucleosides. While this manuscript was in preparation, Chen and co‐workers used an identical approach to identify these same strains as producers of 1 and related fluoronucleosides [34] . We show that while these strains are closely related to S. calvus , they are more than 30‐times better producers of fluoronucleosides, and therefore serve as ideal strains for biosynthetic studies.…”