Wide Distribution of Foxicin Biosynthetic Gene Clusters in Streptomyces Strains – An Unusual Secondary Metabolite with Various Properties

Abstract

Streptomyces diastatochromogenes Tü6028 is known to produce the polyketide antibiotic polyketomycin. The deletion of the pokOIV oxygenase gene led to a non-polyketomycin-producing mutant. Instead, novel compounds were produced by the mutant, which have not been detected before in the wild type strain. Four different compounds were identified and named foxicins A–D. Foxicin A was isolated and its structure was elucidated as an unusual nitrogen-containing quinone derivative using various spectroscopic methods. Through genome mining, the foxicin biosynthetic gene cluster was identified in the draft genome sequence of S. diastatochromogenes. The cluster spans 57 kb and encodes three PKS type I modules, one NRPS module and 41 additional enzymes. A foxBII gene-inactivated mutant of S. diastatochromogenes Tü6028 ΔpokOIV is unable to produce foxicins. Homologous fox biosynthetic gene clusters were found in more than 20 additional Streptomyces strains, overall in about 2.6% of all sequenced Streptomyces genomes. However, the production of foxicin-like compounds in these strains has never been described indicating that the clusters are expressed at a very low level or are silent under fermentation conditions. Foxicin A acts as a siderophore through interacting with ferric ions. Furthermore, it is a weak inhibitor of the Escherichia coli aerobic respiratory chain and shows moderate antibiotic activity. The wide distribution of the cluster and the various properties of the compound indicate a major role of foxicins in Streptomyces strains.

Engineering Pseudochelin Production in Myxococcus xanthus

“…The occurrence of siderophore pathways in taxonomically distinct bacteria is not without precedence, as exemplified by the yersiniabactin locus (39). This wide distribution is usually attributed to lateral gene transfer and a strong evolutionary driving force to maintain the newly acquired biosynthesis genes (39). As expected, myxobacteria predominate among the myxochelin producers (see Fig.…”

“…Biosynthetic genes for the production of myxochelin-type molecules are found in several bacterial lineages, according to an analysis of genomic data. The occurrence of siderophore pathways in taxonomically distinct bacteria is not without precedence, as exemplified by the yersiniabactin locus (39). This wide distribution is usually attributed to lateral gene transfer and a strong evolutionary driving force to maintain the newly acquired biosynthesis genes (39).…”

Profile of PKS and NRPS Gene Clusters in the Genome of Streptomyces cellostaticus NBRC 12849T

“…The genome encoded ten type-I PKS gene clusters (t1pks), one type-II PKS gene cluster (t2pks) and one type-III PKS gene cluster (t3pks), one NRPS gene cluster (nrps) and eight hybrid PKS/NRPS gene clusters (pks/nrps) as listed in Table S1. These numbers were compared with those of PKS and NRPS gene clusters in the Streptomyces strains that we sequenced the whole genomes of in previous studies such as cited ones [12,15,16] (Figure 3). S. cellostaticus NBRC 12849 T has the fewest NRPS gene clusters (pink bar).…”

“…Cluster 3 was a pks/nrps (Figure 4iii) and identified as a biosynthetic gene cluster (BGC) for foxicin (Figure 5c) based on the similarity to the fox gene cluster [15].…”

Absolute configuration of an axially chiral sulfonate determined from its optical rotatory dispersion, electronic circular dichroism, and vibrational circular dichroism spectra

“…The closeness of DF similarity scores with and without normalization indicates a corresponding closeness among the magnitudes of intensities in the calculated and experimental ratio spectra. This method was applied to a number of small molecules to aid in the determination of their ACs …”