Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108

Abstract

Streptomycetes represent an important reservoir of active secondary metabolites with potential applications in the pharmaceutical industry. The gene clusters responsible for their production are often cryptic under laboratory growth conditions. Characterization of these clusters is therefore essential for the discovery of new microbial pharmaceutical drugs. Here, we report the identification of the previously uncharacterized nybomycin gene cluster from the marine actinomycete Streptomyces albus subsp. chlorinus through its heterologous expression. Nybomycin has previously been reported to act against quinolone-resistant Staphylococcus aureus strains harboring a mutated gyrA gene but not against those with intact gyrA. The nybomycin-resistant mutants generated from quinolone-resistant mutants have been reported to be caused by a back-mutation in the gyrA gene that restores susceptibility to quinolones. On the basis of gene function assignment from bioinformatics analysis, we suggest a model for nybomycin biosynthesis.

Identification and Heterologous Expression of the Albucidin Gene Cluster from the Marine Strain Streptomyces Albus Subsp. Chlorinus NRRL B-24108

“…The previously constructed BAC library of Streptomyces albus subsp. chlorinus NRRL B-24108 was used [14]. DNA manipulation, E. coli transformation and E. coli/Streptomyces intergeneric conjugation were performed according to standard protocols [11,12,15].…”

“…The genomic sequence of the albucidin producer S. albus subsp. chlorinus NRRL B-24108 was deposited in GenBank under accession number VJOK00000000 [14].…”

“…To prove this, a BAC 1K1_alb_act was constructed containing only albA-C genes under the control of a strong promoter. The genes downstream of the albA-C operon (genes 18-28) were substituted with the ampicillin resistance gene and the genes upstream of the operon (genes [1][2][3][4][5][6][7][8][9][10][11][12][13][14] were substituted with the hygromycin resistance gene (Figure 1c). The hygromycin resistance gene used was under the control of the strong synthetic promoter TS81 and did not contain a terminator at its 3'-end [21].…”

Benzanthric Acid, a Novel Metabolite From Streptomyces albus Del14 Expressing the Nybomycin Gene Cluster

“…The marine strain Streptomyces albus subsp. chlorinus NRRL B-24108 is responsible for the production of bioactive metabolites such as the herbicide albucidin and the antibiotic nybomycin (Hahn et al, 2009;Rodriguez Estevez et al, 2018). We have recently discovered the biosynthetic genes for nybomycin (nyb genes) in S. albus subsp.…”

“…We have recently discovered the biosynthetic genes for nybomycin (nyb genes) in S. albus subsp. chlorinus through a heterologous expression approach using the chassis strain Streptomyces albus Del14 as a host (Rodriguez Estevez et al, 2018).…”