page_title: Colistin
section_title: Biosynthesis
hierarchical_section_title: Colistin / Biosynthesis
caption_attribution_description: English: Biosyntehsis of colistin
context_page_description: Colistin, also known as polymyxin E, is an antibiotic used as a last-resort for multidrug-resistant Gram negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in a form which can be injection into a vein or muscle or inhaled, known as colistimethate sodium and one which is applied to the skin or taken by mouth, known as colistin sulfate. Resistance to colistin is beginning to appear as of 2017.
  Common side effects of the injectable form include kidney and neurological problems. Other serious side effects may include anaphylaxis, muscle weakness, and Clostridium difficile-associated diarrhea. The inhaled form may result in constriction of the bronchioles. It is unclear if use during pregnancy is safe for the baby. Colistin is in the polymyxin class of medications. It works by breaking down the cytoplasmic membrane which generally results in bacterial cell death.
  Colistin was discovered in 1947 and colistimethate sodium was approved for medical use in the United States in 1970. It is on the World Health Organization's List of Essential Medicines.
context_section_description: The biosynthesis of colistin requires the use of three amino acids threonine, leucine, and 2,4-diaminobutryic acid. It is important to synthesis the linear form of colistin before cycliziation. Elongation of non ribosomal peptide biosynthesis begins by a loading module and then the addition of each subsequent amino acid. The subsequent amino acids are added with the help of an adenylation domain (A), a peptidyl carrier protein domain (PCP), an epimerization domain (E), and a condensation domain (C). Cyclization is accomplished by utilizing a thioesterase. The first step is to have a loading domain, 6-methyl-heptanoic acid, associate with the A and PCP domains. Now with a C, A, and PCP domain that is associated with 2,4-diaminobutryic acid. This continues with each amino acid until the linear peptide chain is completed. The last module will have a thioesterase to complete the cyclization and form the product colistin.
caption: The salmon color refers to the loading domain 6-methyl-heptanoic acid, yellow is 2,4-diaminobutryic acid, light blue is threonine, and purple is leucine
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