Asset Details
Do you wish to reserve the book?
Seven enzymes create extraordinary molecular complexity in an uncultivated bacterium
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Seven enzymes create extraordinary molecular complexity in an uncultivated bacterium
Do you wish to request the book?
Seven enzymes create extraordinary molecular complexity in an uncultivated bacterium
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Seven enzymes create extraordinary molecular complexity in an uncultivated bacterium
2017
Overview
Uncultivated bacteria represent a massive resource of new enzymes and bioactive metabolites, but such bacteria remain functionally enigmatic. Polytheonamides are potent peptide cytotoxins produced by uncultivated bacteria that exist as symbionts in a marine sponge. Outside glycobiology, polytheonamides represent the most heavily post-translationally modified biomolecules that are derived from amino acids. The biosynthesis of polytheonamides involves up to 50 site-specific modifications to create a membrane-spanning β-helical structure. Here, we provide functional evidence that only seven enzymes are necessary for this process. They iteratively catalyse epimerization, methylation and hydroxylation of diverse amino acids. To reconstitute
C
-methylation, we employed the rarely used heterologous host
Rhizobium leguminosarum
to invoke the activities of two cobalamin-dependent
C
-methyltransferases. We observed 44 of the modifications to systematically unravel the biosynthesis of one of the most densely modified and metabolically obscure ribosome-derived molecules found in nature.
Polytheonamides are giant peptide toxins produced by the uncultivated sponge bacterium
Entotheonella factor
. The biosynthesis of polytheonamides involves up to 50 post-translational modifications. Now, heterologous expression in
Escherichia coli
and
Rhizobium
hosts have shown that a minimalistic, iterative enzyme set introduces this exceptional molecular complexity via epimerizations,
C
-/
N
-methylations, hydroxylations, dehydration and proteolytic maturation.
