Isolation, structure, and antibacterial activities of lucensimycins D-G, discovered from Streptomyces lucensis MA7349 using an antisense strategy

J Nat Prod. 2009 Mar 27;72(3):345-52. doi: 10.1021/np8005106.


Bacterial resistance to existing antibiotics continues to grow, necessitating the discovery of new compounds of this type. Antisense-based whole-cell target-based screening is a new and highly sensitive antibiotic discovery approach that has led to a number of new natural product antibiotics. Screening with a rpsD-sensitized strain led to the discovery of a number of natural product polyketides from Streptomyces lucensis. Complete workup of the fermentation extract of this strain allowed for the isolation of seven new compounds, lucensimycins A-G (1-3, 4a, 5-7), with varying degrees of antibacterial activities. Lucensimycin E (5) exhibited the best activity and showed MIC values of 32 microg/mL against Staphylococcus aureus and 8 microg/mL against Streptococcus pneumoniae. The isolation, structure elucidation, and antibacterial activities of four new members, lucensimycins D-G, are described. Lucensimycins D (4a) and E (5) are N-acetyl-l-cysteine adducts of lucensimycin A (1). Semisynthesis of lucensimycins D and E from lucensimycin A has also been described. Lucensimycins F and G are myo-inositolyl-alpha-2-amino-2-deoxy-l-idosyl amide derivatives of lucensimycins D and E, respectively. The relative configuration of these compounds was determined, in part, by molecular dynamics simulations.

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / isolation & purification
  • Anti-Bacterial Agents* / pharmacology
  • DNA, Antisense / genetics
  • DNA, Bacterial / genetics*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Spiro Compounds* / chemistry
  • Spiro Compounds* / isolation & purification
  • Spiro Compounds* / pharmacology
  • Staphylococcus aureus / drug effects
  • Streptococcus pneumoniae / drug effects
  • Streptomyces / chemistry*
  • Streptomyces / genetics*
  • West Indies


  • Anti-Bacterial Agents
  • DNA, Antisense
  • DNA, Bacterial
  • Spiro Compounds
  • lucensimycin A