RT @ACSCentSci: Grab ‘n go: siderophore-binding proteins provide pathogens a quick fix to satisfy their hunger for iron!. Read #FirstRxns h….

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RT @ucsantabarbara: .@UCSB_chemistry’s graduate students recently discovered a technique to decipher siderophore's 3D structure. A better u….

"Mentoring: Reflections and Suggestions" -- Don't miss this editorial by Harry Gray, pioneer of #bioinorganic chemistry. Alison is a proud member of Gray Nation!.

We're lucky to have Rich in our department!.

Cool! Drosophila melanogaster has a nonribosomal peptide synthetase! .

#UCSB colleagues, sign ups are open for the 2019 Out List! Please consider coming out as member of the LGBTQIA community, or even as a supporter. Visibility matters!. @ucsantabarbara @ucsb_rcsgd .

RT @Chemjobber: When you finish a PhD in chemistry they take you in a special room and tell you that tenure-track professorships aren't rea….

When you finish a PhD in chemistry they take you in a special room and tell you that the periodic table isn't real and all matter is just made of the elements earth, air, fire, and water. I am posting this at great physical risk to myself and my family.

To sum up, we can now predict the residue selectivity and stereospecificity of any siderophore β-hydroxylase. Although mechanistic questions remain, structures can now quickly be predicted just by looking at the gene cluster, or better yet, by using the pHMMs provided. (11/11).

To confirm that we could actually use these trees to predict siderophore structures, Cliff, Jae, and Jean isolated four siderophores and stereochemically characterized the OHAsp residues. Each matched the subtype-based prediction! (10/11).

That still left the question of stereochemistry. Mapping reported OHAsp stereochemistries to our phylogenetic tree revealed that the IβH family of NRPS domains is selective for 3S hydroxylation, while the TβH family of standalone enzymes is selective for 3R hydroxylation! (9/?)

The reconstructed phylogenetic tree of β-hydroxylases shows that the functional subtypes we identified are true evolutionary subtypes that have diverged in reactivity over time. (8/?)

The IβH_Asp family of NRPS domain hydroxylases is found alongside a "broken" condensation domain that lacks a catalytic motif. Instead of condensation, we think that this "Interface" domain is responsible for bringing together two NRPS enzymes so hydroxylation can occur. (7/?)

Each type of β-hydroxylase is associated with a different NRPS domain that seems to be required for hydroxylation. When those domains are absent, no hydroxylation occurs. We also identified a family of histidine β-hydroxylases involved in siderophore biosynthesis. (6/?)

We collected over 30 siderophore biosynthetic gene clusters, looking for patterns in reactivity. Turns out, there are two different types of β-hydroxylases. One is a standalone enzyme, and the other is a NRPS domain fused to the rest of the NRPS machinery. (5/?).

Further complicating things, OHAsp has four possible stereoisomers, three of which have been identified in siderophores. We set out to develop new genomic tools that we could use to predict both which Asp residues get hydroxylated, and with what stereochemistry. (4/?).

Aspartate is hydroxylated by a class of non-heme iron(II)/α-ketoglutarate dependent β-hydroxylases. Unfortunately, a β-hydroxylase in the gene cluster doesn't mean that every Asp residue will be hydroxylated in the final siderophore. (3/?)

OHAsp-containing siderophores are peptidic, but aren't made by the ribosome directly. Instead, the peptide is synthesized by a huge multi-domain enzyme called a nonribosomal peptide synthetase (NRPS, we pronounce it 'nerps'), which works like an assembly line. (2/?)

The lead author, Zach Reitz, is here to explain their work!. Siderophores are small molecule chelators that bacteria produce to acquire iron from their environment. One common functional group that provides coordination to Fe(III) is β-hydroxyaspartate (OHAsp). (1/?).