Pyocheline

Sun G-X, W-Q Zhou, J-J Zhong (2006) Organotin decomposition by pyochelin secreted by Pseudomonas aeruginosa even in an iron-sufficient environment. Appl Environ Microbiol 72 6411-6413. 

S. Buysens, K. Heungens, J. Poppe, and M. Hofte, Involvement of pyochelin and pyoverdin in suppression of Pyt/r/wm-induced damping-off of tomato by Pseudomo-na. i aeruginosa 7NSK2. Appl. Environ. Microbiol. 62 865 (1996). 

Fig. 22. Pyochelin (60) and the ternary complex formed with ferric iron, pyochelin, and cepabactin (61).

The oxidation state of thiazolines and oxazolines can be adjusted by additional tailoring enzymes. For instance, oxidation domains (Ox) composed of approximately 250 amino acids utilize the cofactor FMN (flavin mononucleotide) to form aromatic oxazoles and thiazoles from oxazolines and thiazolines, respectively. Such domains are likely utilized in the biosynthesis of the disorazoles, " diazonimides, bleomycin, and epothiolone. The typical domain organization for a synthetase containing an oxidation domain is Cy-A-PCP-Ox however, in myxothiazol biosynthesis one oxidation domain is incorporated into an A domain. Alternatively, NRPSs can utilize NAD(P)H reductase domains to convert thiazolines and oxazolines into thiazolidines and oxazolidines, respectively. For instance, PchC is a reductase domain from the pyochelin biosynthetic pathway that acts in trans to reduce a thiazolyinyl-Y-PCP-bound intermediate to the corresponding thiazolidynyl-Y-PCP. ... 

The three omibactins are accompanied by minor components, which contain an additional oxygen atom. Their structure has not been investigated. Omibactins are the main siderophores of a series of Burkholderia strains accompanied in part by pyochelin (Sect. 5) and cepabactin (Sect. 6) (235). A furthers, cepacia siderophore is cepaciachelin (Sect. 3.2) (15). The iron acquisition by the various siderophores of B. cepacia has been discussed in detail (359). 

The stmcture of pyochelin (for a detailed bibliography, see (57)), a secondary siderophore of Pseudomonas aeruginosa and of Burkholderia cepacia was established (75) as 2-(2-o-hydroxyphenyl-2-thiazolin -yl)-3-methylthiazolidine-4-carboxylic acid. It consists of a mixture of two easily interconvertible stereoisomers (pyochelin I and II) differing in the configuration of C-2". They can be separated by chromatography, but in methanolic solution (not in DMSO) the equilibrium (ca. 3 1) is restored quickly. For a discussion of the mechanism of isomerization, see (57, 577). 

Pyochelin is a non-ribosomal condensation product of salicyhc acid with two molecules of cysteine (289). Intermediates with one cysteine unit are aeruginoic acid (Fig. 21, 67) first isolated from Pseudomonas aeruginosa (390), and (-l-)-(5)-4,5-dihydroaeruginoic acid, from Pseudomonas fluorescens (57). Detailed studies (274a) suggest that M-hydroxybenzoyl-L-cysteine bound to the synthetase... 

Micacocidin (Fig. 22, 68) from Pseudomonas sp. complexes Fe " and other metal ions 189,190). Whether it acts as a siderophore has not been investigated. A stereospecific synthesis was elaborated 161,161a), but the same isomerization problems at C-4 and C-2" were encountered as had been observed with pyochelin (see Note 14 in 161)). 

Ankenbauer RG, Toyokuni T, Staley A, Rinehard KL Jr, Cox CD (1988) Synthesis and Biological Activity of Pyochelin, a Siderophore of Pseudomonas aeruginosa. J Bacteriol 170 5344... 

Cox CD, Rinehart KL Jr, Moore ML, Cook, JC Jr (1981) Pyochelin Novel Structure of an Iron-chelating Growth Promotor for Pseudomonas aeruginosa. Proc Natl Acad Sci USA 78 4256... 

Hayen H, Volmer DA (2006) Different Iron-chelating Properties of Pyochelin Diastereo-isomers Revealed by LC/MS. Anal Bioanal Chem 385 606... 

Klumpp C, Burger A, Mislin GL, Abdallah MA (2005) From a Total Synthesis of Cepa-bactin and its 3 1 Ferric Complex to the Isolation of a 1 1 1 Mixed Complex between Iron (111), Cepabactin and Pyochelin. Bioorg Med Chem Lett 15 1721... 

Quadri LEN, Keating TA, Patel HM, Walsh CT (1999) Assembly of Pseudomonas aeruginosa Nonribosomal Peptide Siderophore Pyochelin in vitro Reconstitution of Aryl-4, 2-bisthiazoline Synthetase Activity from PchD, PchE, and PChF. Biochemistry 38 14941... 

Schlegel K, Taraz K, Budzikiewicz H (2004) The Stereoisomers of Pyochelin, a Side-rophore of Pseudomonas aeruginosa. BioMetals 17 409... 

Youard ZA, Mislin GLA, Majcherczyk PA, Schalk U, Reimmarm C (2007) Pseudomonas fluorescens CHAO Produces enantio-Pyochelin, the Optical Antipode of the Pseudomonas aeruginosa Siderophore Pyochelin. J Biol Chem 282 35546... 

Zamri A, Abdallah MA (2000) An Improved Stereocontrolled Synthesis of Pyochelin, Siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. Tetrahedron 56 249... 

In NRPS, the cyclization domain catalyzes cyclization of the side-chain nucleophile from a dipeptide moiety such as AA-Ser or AA-Cys (AA = amino acids) to form a tetrahedral intermediate, followed by dehydration to form oxazolines and thiazolines (Scheme 7.1) [20]. The synthesis of a 2-methyl oxazoline from threonine follows a similar mechanism. Once a heterocycle is formed, it can be further modified by reductase to form tetrahydro thiazolidine in the case of pyochelin biosynthesis. Conversely, oxidation of the dehydroheterocycles lead to heteroaro-mahc thiazoles or oxazoles as in the case of epothilone D (Figure 7.2) [21]. 

Figure 16-1 Structures of several siderophores and of their metal complexes. (A) Enterobactin of E. coli and other enteric bacteria 12 (B) parabactin (R = H) from Paracoccus denitrijkans and agrobactin (R = OH) from Agrobacterium tumefaciens 20 (C) ferrichrome 9 (D) pyochelin from Pseudomonas aeruginosa.21...

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