Streptomyces sp. VN1, a producer of diverse metabolites including non-natural furan-type anticancer compound

Abstract

Streptomyces sp. VN1 was isolated from the coastal region of Phu Yen Province (central Viet Nam). Morphological, physiological, and whole genome phylogenetic analyses suggested that strain Streptomyces sp. VN1 belonged to genus Streptomyces. Whole genome sequencing analysis showed its genome was 8,341,703 base pairs in length with GC content of 72.5%. Diverse metabolites, including cinnamamide, spirotetronate antibiotic lobophorin A, diketopiperazines cyclo-L-proline-L-tyrosine, and a unique furan-type compound were isolated from Streptomyces sp. VN1. Structures of these compounds were studied by HR-Q-TOF ESI/MS/MS and 2D NMR analyses. Bioassay-guided purification yielded a furan-type compound which exhibited in vitro anticancer activity against AGS, HCT116, A375M, U87MG, and A549 cell lines with IC 50 values of 40.5, 123.7, 84.67, 50, and 58.64 µM, respectively. In silico genome analysis of the isolated Streptomyces sp. VN1 contained 34 gene clusters responsible for the biosynthesis of known and/or novel secondary metabolites, including different types of terpene, T1PKS, T2PKS, T3PKS, NRPS, and hybrid PKS-NRPS. Genome mining with HR-Q-TOF ESI/MS/MS analysis of the crude extract confirmed the biosynthesis of lobophorin analogs. This study indicates that Streptomyces sp. VN1 is a promising strain for biosynthesis of novel natural products. Natural products (NPs) have been starting points of drug discovery for several decades. Major antimicrobials and chemotherapeutics entering clinical trials are often based on NPs 1,2. Drugs with a natural origin can be produced as primary or secondary metabolites from versatile living organisms. Different microorganisms such as Streptomyces, myxobacteria and uncultured bacteria are major sources of such beneficial NPs 3,4. Moreover, different metabolic engineering approaches and sophisticated techniques employing systems biology or synthetic biology can assist in harnessing the full potential of these bacteria in terms of productivity or creating diverse products 5,6. Hence, there is renewed interest in mining microorganisms for new leads owing to the remarkable success of microbial metabolites as starting points for developing effective antibiotics, anticancer agents, and agrochemicals 7. Streptomyces are Gram-positive, aerobic bacteria in the order of Actinomycetales within the class of Actinobacteria. Genus Streptomyces was first proposed by Waksman and Henrici in 1943. It was classified into the family of Streptomycetaceae based on its morphology and cell wall chemotype 8. Previous studies have shown that more than 74% of current antibiotics are derived from the genus Streptomyces 9. Using integrated approaches of compound screening and drug development, Streptomyces arsenal has been found to be able to combat antibiotic resistance 5. Multiple approaches such as ribosome engineering 10 and genome mining 11 have been used to find new secondary metabolites in old Streptomyces strains. Besides the effort to work on old strains to explore novel biosynthetic gene clusters (BGCs),...

Evaluation of Antimicrobial and Antiproliferative Activities of Actinobacteria Isolated From the Saline Lagoons of Northwest Peru

“…Compound 6 exhibited fragments at m/z 168.07, 167.07 and 153.05, in agreement with the literature (Nguyen et al 2020). Compound 6 was reported as a secondary metabolite of the Streptomyces sp .…”

“…Also, MS/MS profile of compound 2 presented m/z 883.49 and 753.43 (Fig. S5), related to the loss of the sugar units in the structure, according with the literature (Nguyen et al 2020). Similar as observed in cluster A, cluster B also exhibited other lobophorin compounds such as lobophorins B, E and K that were identified based on their accurate masses and fragmentation profiles with typical fragments at m/z 184.09, 157.09, 108.08 and 97.06 (Fig.…”

Vertical Stratification in Urban Green Space Aerobiomes

“…With the exception of Flavobacterium, species in these genera are considered to have potentially beneficial or pathogenic impacts on human health. For example, the Actinobacteria Streptomyces spp., is considered to be a microbial "old friend" and potentially beneficial to human health via production and regulation of antiproliferative, antiinflammatory and antibiotic compounds (Bolourian and Mojtahedi 2018;Nguyen et al 2020). This genus had higher relative abundance at lower sampling heights.…”

Draft Genome Sequence of Streptomyces sp. Strain BR123, Endowed with Broad-Spectrum Antimicrobial Potential

“…Streptomyces members are aerobic, Gram-positive filamentous bacteria belonging to the order Actinomycetales of Actinobacteria . Bacteria in this genus are well reported for their production of bioactive secondary metabolites that have great biofunctional diversity and different applications, such as antibacterial, antifungal, antiviral, anticancer, immunosuppressant, insecticidal, and herbicidal, which make them suitable for use as pharmaceuticals and in agricultural industries ( 1 – 4 ). More than 7,630 bioactive secondary metabolites have been reported to be produced only by Streptomyces spp.…”