Katanosin Explained

Katanosins are a group of antibiotics (also known as lysobactins). They are natural products with strong antibacterial potency.^[1] So far, katanosin A and katanosin B (lysobactin) have been described.

Sources

Katanosins have been isolated from the fermentation broth of microorganisms, such as Cytophaga.^[2] or the Gram-negative bacterium Lysobacter sp.^[3]

Structure

Katanosins are cyclic depsipeptides (acylcyclodepsipeptides). These non-proteinogenic structures are not ordinary proteins derived from primary metabolism. Rather, they originate from bacterial secondary metabolism. Accordingly, various non-proteinogenic (non-ribosomal) amino acids are found in katanosins, such as 3-hydroxyleucine, 3-hydroxyasparagine, allothreonine and 3-hydroxyphenylalanine. All katanosins have a cyclic and a linear segment (“lariat structure”). The peptidic ring is closed with an ester bond (lactone).

Katanosin A and B differ in the amino acid position 7. The minor metabolite katanosin A has a valine in this position, whereas the main metabolite katanosin B carries an isoleucine.

Biological activity

Katanosin antibiotics target the bacterial cell wall biosynthesis.^[4] They are highly potent against problematic Gram-positive hospital pathogens such as staphylococci and enterococci. Their promising biological activity attracted various biological and chemical research groups. Their in-vitro potency is comparable with the current “last defence” antibiotic vancomycin.

Chemical synthesis

The first total syntheses of katanosin B (lysobactin) have been described in 2007.^{[5] [6]}

References

1. 3209466 . 1988 . Bonner . DP . O'Sullivan . J . Tanaka . SK . Clark . JM . Whitney . RR . Lysobactin, a novel antibacterial agent produced by Lysobacter sp. II. Biological properties . 41 . 12 . 1745–51 . The Journal of Antibiotics . 10.7164/antibiotics.41.1745. free .
2. 3209465 . 1988 . O'Sullivan . J . McCullough . JE . Tymiak . AA . Kirsch . DR . Trejo . WH . Principe . PA . Lysobactin, a novel antibacterial agent produced by Lysobacter sp. I. Taxonomy, isolation and partial characterization . 41 . 12 . 1740–4 . The Journal of Antibiotics . 10.7164/antibiotics.41.1740. free .
3. 3403364 . 1988 . Shoji . J . Hinoo . H . Matsumoto . K . Hattori . T . Yoshida . T . Matsuura . S . Kondo . E . Isolation and characterization of katanosins a and B . 41 . 6 . 713–8 . The Journal of Antibiotics . 10.7164/antibiotics.41.713. free .
4. 10.1021/jacs.5b11807 . The Mechanism of Action of Lysobactin . 2016 . Lee . Wonsik . Schaefer . Kaitlin . Qiao . Yuan . Srisuknimit . Veerasak . Steinmetz . Heinrich . Müller . Rolf . Kahne . Daniel . Walker . Suzanne . Journal of the American Chemical Society . 138 . 1 . 100–103 . 26683668 . 4817722 .
5. 17211904 . 2007 . Von Nussbaum . F . Anlauf . S . Benet-Buchholz . J . Häbich . D . Köbberling . J . Musza . L . Telser . J . Rübsamen-Waigmann . H . Brunner . NA . Structure and total synthesis of lysobactin (katanosin B) . 46 . 12 . 2039–42 . 10.1002/anie.200604232 . Angewandte Chemie International Edition in English .
6. 17432854 . 2007 . Guzman-Martinez . A . Lamer . R . Vannieuwenhze . MS . Total synthesis of lysobactin . 129 . 18 . 6017–21 . 10.1021/ja067648h . 2151959 . Journal of the American Chemical Society.