Genome mining Streptomyces sp. KCTC 0041BP as a producer of dihydrochalcomycin

Appl Microbiol Biotechnol. 2021 Jun;105(12):5023-5037. doi: 10.1007/s00253-021-11393-w. Epub 2021 Jun 17.

Abstract

Streptomyces sp. KCTC 0041BP, which was isolated from a soil sample in Cheolwon, Republic of Korea, is a dihydrochalcomycin producer. In this study, we obtained the genome of S. sp. KCTC 0041BP with 7.54 Mb genome size. antiSMASH and the dbCAN2 meta server predicted that the genome would contain 26 secondary metabolite biosynthetic gene clusters (BGCs) and 285 carbohydrate-active enzymes. Besides dihydrochalcomycin, 21 compounds were successfully identified from S. sp. KCTC 0041BP, and among them, the structure of 8 compounds were proven by high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance (NMR). The identification of chalcomycin analogs led to a better understanding of the biosynthetic pathway of dihydrochalcomycin/chalcomycin. From the analysis of cluster 2 and solvent selection, linearmycins were determined. Linearmycins showed antibacterial activity with both Gram-positive and Gram-negative bacteria and antifungal activity. One strain many compounds (OSMAC) strategy was applied to activate the salicylic acid production in this strain. A salicylic acid biosynthetic pathway was also predicted, but not by antiSMASH. These results showed that this strain can produce many useful compounds and potentially produce novel compounds with most secondary BGCs yet to be experimentally identified.

Keywords: Bioactive compounds; Biosynthetic gene clusters; Genome mining; Natural products; Streptomyces.

MeSH terms

  • Anti-Bacterial Agents
  • Glycosides
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Macrolides
  • Multigene Family
  • Republic of Korea
  • Streptomyces* / genetics

Substances

  • Anti-Bacterial Agents
  • Glycosides
  • Macrolides
  • dihydrochalcomycin