tabtoxin

Tabtoxin resistance protein (TTR) is an enzyme that catalyzes the acetylation of TBL, rendering tabtoxin-producing pathogens tolerant to their own phytotoxins. The structure of an inactivated mutant of TTR is solved with its natural cofactor acetyl-CoA to 1.55 Å resolution. The binary complex forms a characteristic “V” shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs).{{cite journal|title=Site-Directed Mutagenesis and Preliminary X-Ray Crystallographic Studies of the Tabtoxin Resistance Protein|first=Yi Ding, Shentao Li, Xiaofeng Li, Fei Sun, Jinyuan Liu, Nanming Zhao and Zihe |last=Rao|date=31 May 2003|journal=Protein and Peptide Letters|volume=10|issue=3|pages=255–63|pmid=12871145|doi=10.2174/0929866033478924}} There are reports that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

The production of tabtoxin itself is also part of the self-resistance strategy. These pathogens produce TBL before tabtoxin is produced; to detoxify, the enzyme TblF links TBL to threonine (Thr), producing a non-toxic product.{{cite journal |last1=Wencewicz |first1=TA |last2=Walsh |first2=CT |title=Pseudomonas syringae self-protection from tabtoxinine-β-lactam by ligase TblF and acetylase Ttr. |journal=Biochemistry |date=2 October 2012 |volume=51 |issue=39 |pages=7712–25 |doi=10.1021/bi3011384 |pmid=22994681}}

{{missing information|section|TabD, ... ({{PMID|16506699}} and {{PMID|29307827}} would be useful but are both paywalled)|date=March 2022}}

The biosynthetic precursors of tabtoxin were identified by the incorporation of 13C-labeled compounds. L-threonine and L-aspartate make up the side chain, while pyruvic acid and the methyl group of L-methionine make up β-lactam moiety. A biosynthetic model for the formation of TβL resembles that of lysine, where the first dedicated step is the DapA-catalyzed condensation of aspartic acid semialdehyde with pyruvate to form L-2,3-dihydropicolinate (DHDPA). Tabtoxin biosynthesis branches off from the lysine biosynthetic pathway before the formation of diaminopimelate (DAP).{{efn|As additional evidence for this pathway, DapB (Dihydrodipicolinate reductase), a step between DHDPA and DAP, is required to produce both lysine and tabtoxin.}} The 31-kb biosynthetic cluster consists of:

• TabA ({{UniProt|P31851}}), an enzyme related to lysA (diaminopimelate decarboxylase)
• TabB ({{UniProt|P31852}}), an enzyme related to dapD (THDPA succinyl-CoA succinyltransferase, THDPA-ST)
• TblA ({{UniProt|P31850}}), an enzyme with no close paralogs (identified as a member of SAMe-dependent methyltransferase superfamily by InterPro)

This pathway produces TBL; the enzyme TblF finalize the synthesis by linking TBL to Thr to form tabtoxin.{{efn|TblF is able to distinguish between TBL and the spontaneously-formed isomer TDL (tabtoxinine-δ-lactam). It also produces no "reversed" peptides.}}{{cite journal|title=Pseudomonas syringae Phytotoxins: Mode of Action, Regulation, and Biosynthesis by Peptide and Polyketide Synthetases|first1=Carol L.|last1=Bender|first2=Francisco|last2=Alarcón-Chaidez|first3=Dennis C.|last3=Gross|date=1 June 1999|journal=Microbiol. Mol. Biol. Rev.|volume=63|issue=2|pages=266–292|pmid=10357851|pmc=98966|doi=10.1128/MMBR.63.2.266-292.1999}}

The effects of carbon, nitrogen sources and amino acids on growth and tabtoxin production by pv. tabaci, were examined by varying the components of a defined basal medium, which contained the following nutrients per liter: sucrose (10 g), KNO₃ (5 g), MgSO₄.7H₂O (0.2 g), CaCl₂.2H₂O (0.11 g), FeSO₄.7H₂O (20 mg), NaH₂PO₄.2H₂O (0.9 g) and H₂PO₄.3H₂O{{clarify|date=November 2021}} (1 g). Both growth and quantity of tabtoxin synthesized were significantly affected by carbon source, nitrogen source and amino acid supplements. Sorbitol, xylose and sucrose proved to be the best carbon sources for tabtoxin production. Specific toxin production was very low using glucose as a single carbohydrate source, although bacterial growth was well supported by glucose. Amount and type of nitrogen sources (NH₄Cl or KNO₃) affected the growth of pv. tabaci and quantities of tabtoxin produced. Nitrate is the best of these two forms of nitrogen for production of tabtoxin.

Some progress has been made on elucidating factors that regulate tabtoxin biosynthesis in P. syringae.

Zinc was shown to be required for the aminopeptidase activity, which hydrolyzes tabtoxin to release TβL.

{{notelist}}

{{reflist}}

• http://aem.asm.org/content/79/16/5023.long
• {{cite journal | doi=10.1016/S0022-2836(02)01284-6 | pmid=12527305 | volume=325 | issue=5 | title=Crystal Structure of Tabtoxin Resistance Protein Complexed with Acetyl Coenzyme A Reveals the Mechanism for β-Lactam Acetylation | journal=Journal of Molecular Biology | pages=1019–1030| year=2003 | last1=He | first1=Hongzhen | last2=Ding | first2=Yi | last3=Bartlam | first3=Mark | last4=Sun | first4=Fei | last5=Le | first5=Yi | last6=Qin | first6=Xincheng | last7=Tang | first7=Hong | last8=Zhang | first8=Rongguang | last9=Joachimiak | first9=Andrzej | last10=Liu | first10=Jinyuan | last11=Zhao | first11=Nanming | last12=Rao | first12=Zihe }}

Category:Alpha-Amino acids

Category:Amino acid derivatives

Category:Bacterial toxins

Category:Lactams

Category:Azetidines