Genome mining for unwinding iron binding. #BioInorganic #Chemistry, #Bioinformatics, #Biosynthesis Student run, opinions our own. IG: butlerlabucsb
Santa Barbara, CA
Joined April 2018
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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/?)
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/?)
When your committee member asks that tough question during candidacy and you try to deflect... #phdchat #phdlife (credit @ZachWeiner #smbc)
ALT A man in front of a podium throws a smoke bomb. The audience looks angrily at the man, smoke only up to their necks.
An action-packed day with talks from the 2019 Arthur C. Cope Scholars at #ACSSanDiego!
Come see the Butler lab at #ACSSanDiego! Check out Parker and Cliff's posters at 5:30 this evening, Alison's Cope Scholar Award address on Tuesday, and Zach's talk on Wednesday! @CliffHardy4 @siderophores @UCSB_chemistry
