so you want to know about siderophore synthesis l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
So, you want to know about siderophore synthesis PowerPoint Presentation
Download Presentation
So, you want to know about siderophore synthesis

Loading in 2 Seconds...

play fullscreen
1 / 28

So, you want to know about siderophore synthesis - PowerPoint PPT Presentation


  • 280 Views
  • Uploaded on

So, you want to know about siderophore synthesis. Presented by: Steven Backues Brooks Maki and Donnie Berkholz “The Invisible Man”. Hydroxamic Acid Groups. N-Alkylation of O-substituted Hydroxamic acid.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'So, you want to know about siderophore synthesis' - cree


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
so you want to know about siderophore synthesis

So, you want to know about siderophore synthesis

Presented by:

Steven Backues

Brooks Maki

and

Donnie Berkholz “The Invisible Man”

hydroxamic acid groups
Hydroxamic Acid Groups
  • N-Alkylation of O-substituted Hydroxamic acid.
  • Formation of an oxime from an aldehyde and a hydroxylamine. Followed by reduction and acylation
  • These derivatives allowed synthesis of several siderophores and their analogues
alternative methods
Alternative Methods
  • Oxidation of Lysine and OrnithineWith DMD (dimethyldioxarine)
  • Conversion of primary amines to imines, with oxidation of imines to oxaziridines. Hydrolysis leads to hydroxylamines.
  • D-Ferrichrome synthesized by this method
danoxamine
Danoxamine
  • Composed of a linear series of three hydroxamic acids.
  • Composed of two major groups linked by succinic acid.
biosynthesis of siderophores

Biosynthesis of Siderophores

How it’s really done.

step 1 ornithine n 5 oxygenase
Step 1: Ornithine N5-Oxygenase
  • The formation of the N-O bond is the first committed step in hydroxamate synthesis
  • Ornithine, an amino acid used in the urea cycle, is reacted with O2 and NADPH to give an N-O bond at the end of its side chain.
step 2 n 5 transacylase
Step 2: N5-Transacylase
  • The nitrogen modified in this way is additionally attached to an acyl group carried by coenzyme A
  • This completes the hydroxamate prosthetic group
step 3 non ribosomal peptide synthetase
Step 3: Non-ribosomal Peptide Synthetase
  • This synthetase is a large complex with many subdomains, including an adenylation domain, a thiolation domain, and a condensation domain.
adenylation
Adenylation
  • First, the hydroxamate is is activated by addition of an adenylate group at its C terminus
  • The source of the adenylate group is ATP, and the reaction occurs with production of pyrophosphate
thiolation
Thiolation
  • The hydroxamate group is then transferred to the enzyme through the formation of a thioester linkage with displacement of the adenylate group.
condensation
Condensation
  • Finally, the hydroxamate group is attached to another molecule (perhaps another hydroxamate group, or else a growing chain) by the nucleophilic attack of an OH or NH from the chain on the S-linked carbonyl, displacing the sulfur.
cathechols vibriobactin
Cathechols: Vibriobactin
  • Vibriobactin is a siderophore used by Vibrio cholerae
  • Its synthesis also involves a large, non-ribosomal peptide synthetase, and follows many of the same pathways as the synthesis of hydroxamate siderophores outlined above.
the cathechol prosthetic group
The Cathechol Prosthetic Group
  • The cathechol prosthetic group is 2,3-dihydroxybenzoic acid, which is formed from chorismic acid
nonribosomal peptide synthetase
Nonribosomal Peptide Synthetase
  • 2,3-dihydrobenzoic acid then acts as a substrate for Vibirobactin Syntetase
  • It is first activated by adenylation, then transferred to the enzyme with formation of a thioester
transfer to norspermidine
Transfer to Norspermidine
  • This thioester complex then undergoes nucleophilic attack by a primary amine on norspermidine.
  • The norspermidine/cathechol complex goes on to react with two more cathechol prosthetic groups (these, however, attached by threonine derived linkages) to form the final siderophore
synthesis
Synthesis
  • Although it has neither hydroxamate nor cathechol groups, Yersiniabactin follows some of the same synthesis pathways, using a nonribosomal peptide sythetase that has clear homologies with, for example, vibriobactin sythetase
beginnings
Beginnings
  • Synthesis begins with salicylic acid (2-hydroxy-benzoic acid)
  • This is activated by the attachment of an adenylate group, then loaded onto the enzyme by the formation of a thioester, as before
elongation
Elongation
  • At the same time, two cystines are also activated then loaded onto the same enzyme, also via a thioester linkage
  • Then, in the condensation/cyclization domain, the salicyate group is transferred onto one of the cystines, which is then cyclized.
  • This cyclization is an unusual property of this particular synthetaes
completion
Completion
  • A second cystine is added, and also cyclized, and the resulting molecule undergoes the addition of a malonyl group, S-adenosylmethionine, and an additional cystine to complete the synthesis
overview
Overview:
  • The use of a large, multidomain nonribosomal peptide synthetase was a common element of all of these syntheses.
  • All of these processes included the activation of a substrate by adenylation and the transfer to a thioester linkage with the enzyme, followed by condensation to form a longer chain. This is similar to the process followed in biosynthesis of fatty acids.
references
References
  • Roosenberg, J.M. and Miller, M.J. Total Synthesis of the Siderophore Danoxamine. J. Org. Chem. 2000 Vol. 65 No. 16. 4833 – 4838.
  • Lin, Y. and Miller, M.J. Synthesis of Siderophore Components by and Indirect Oxidation Method. J. Org. Chem. 1999 Vol. 64 No. 20. 7451 – 7458.
  • Gaspar, M., Grazina, R., Bodor, A., Farkas, E., and Santos, M.A. Macrocyclic tetraamine tris(hydroxamate) ligand. J. Chem Soc. 1999 799 – 806.
  • Duhme, A.K. Synthesis of two dioxomolybdenum complexes of a siderophore analogue. J. Chem. Soc. 1997 773 – 778.
  • Atkinson, A. Bacterial Iron Transport. Biochemistry. 1998. 15965 - 15973