Leinamycin is an 18-membered macro
lactam
A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''.
Nomenclature
Greek prefixes in alphabetical order indicate ring size:
* α-Lactam (3-atom rings)
* β-Lacta ...
produced by several species of ''
Streptomyces atroolivaceus
''Streptomyces atroolivaceus'' is a bacterium species from the genus ''Streptomyces
''Streptomyces'' is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of ''Streptomyces'' bacteria ha ...
''. 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
Moiety may refer to:
Chemistry
* Moiety (chemistry), a part or functional group of a molecule
** Moiety conservation, conservation of a subgroup in a chemical species
Anthropology
* Moiety (kinship), either of two groups into which a society is ...
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
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
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.
:
References
{{Reflist
Polyketides