title: Leinamycin
text: # Leinamycin
  
  Leinamycin is an 18-membered macrolactam produced by several species of Streptomyces atroolivaceus. This macrolactam has also been shown to exhibit antitumor properties as well as antimicrobial properties against gram-positive and gram-negative bacteria. The presence of a spiro-fused 1,3-dioxo-1,2-dithiolane moiety was a unique structural property at the time of this compound's discovery and it plays an important role in leinamycin's antitumor and antibacterial properties due to its ability to inhibit DNA synthesis.
  
  ## Biosynthesis
  
  The seminal proposal for the biosynthesis of leinamycin was published in Chemistry & Biochemistry in 2004. This biosynthesis consists of a discrete and modular NRPS, AT-less PKSs, and PKS modules. NRPS-PKS assembly line dictates the loading of D-Ala to initiate biosynthesis, followed by the loading of L-Cys to the peptidyl carrier protein (PCP). The dipeptide is then cyclized and oxidized to form the thiazonyl-S-PCP intermediate. The thiazonyl intermediate is then transferred to the PKS assembly line where the backbone is elongated by six units. The leinamycin hybrid peptide-polyketide carbon backbone intermediate is then cyclized by the thioesterase domain (TE) to yield intermediate 1. Methylmalonyl-CoA then condenses at the beta-keto group of 1, yielding 2. A series of tailoring enzymes converts 2 to 4, presumably through intermediate 3 to complete the biosynthesis of leinamycin.
  
  