Biosynthesis of methyl-proline containing griselimycins, natural products with anti-tuberculosis activity.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractGriselimycins (GMs) are depsidecapeptides with superb anti-tuberculosis activity. They contain up to three (2S,4R)-4-methyl-prolines (4-MePro), of which one blocks oxidative degradation and increases metabolic stability in animal models. The natural congener with this substitution is only a minor component in fermentation cultures. We showed that this product can be significantly increased by feeding the reaction with 4-MePro and we investigated the molecular basis of 4-MePro biosynthesis and incorporation. We identified the GM biosynthetic gene cluster as encoding a nonribosomal peptide synthetase and a sub-operon for 4-MePro formation. Using heterologous expression, gene inactivation, and in vitro experiments, we showed that 4-MePro is generated by leucine hydroxylation, oxidation to an aldehyde, and ring closure with subsequent reduction. The crystal structures of the leucine hydroxylase GriE have been determined in complex with substrates and products, providing insight into the stereospecificity of the reaction.
CitationBiosynthesis of methyl-proline containing griselimycins, natural products with anti-tuberculosis activity. 2017, 8 (11):7521-7527 Chem Sci
AffiliationHelmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Cryptic Production of trans-3-Hydroxyproline in Echinocandin B Biosynthesis.
- Authors: Mattay J, Houwaart S, Hüttel W
- Issue date: 2018 Apr 1
- Conformational preference and cis-trans isomerization of 4-methylproline residues.
- Authors: Kang YK, Byun BJ, Park HS
- Issue date: 2011 Jan
- Characterization of a gene cluster responsible for the biosynthesis of anticancer agent FK228 in Chromobacterium violaceum No. 968.
- Authors: Cheng YQ, Yang M, Matter AM
- Issue date: 2007 Jun
- Biochemical and genetic characterization of fungal proline hydroxylase in echinocandin biosynthesis.
- Authors: Zhang F, Liu H, Zhang T, Pijning T, Yu L, Zhang W, Liu W, Meng X
- Issue date: 2018 Sep
- Evaluation of microbially enhanced soybean meal as an alternative to fishmeal in weaned pig diets.
- Authors: Sinn SM, Gibbons WR, Brown ML, DeRouchey JM, Levesque CL
- Issue date: 2017 May