498-40-8Relevant articles and documents
N-Phenylacetylation and Nonribosomal Peptide Synthetases with Substrate Promiscuity for Biosynthesis of Heptapeptide Variants, JBIR-78 and JBIR-95
Takeda, Kunpei,Kemmoku, Kohei,Satoh, Yasuharu,Ogasawara, Yasushi,Shin-Ya, Kazuo,Dairi, Tohru
, p. 1813 - 1819 (2017/07/26)
JBIR-78 (1) and JBIR-95 (2), both of which are heptapeptide derivatives isolated from Kibdelosporangium sp. AK-AA56, have the same amino acid sequences except for the second amino acid: phenylacetic acid (Paa)-l-Val-d-Asp (1)/d-cysteic acid (2)-l-Ala-(3S)-3-hydroxy-d-Leu-Gly-d-Ala-l-Phe. Heterologous expression of the biosynthetic gene cluster including genes encoding nonribosomal peptide synthetases (NRPS) and in vitro assays with recombinant Orf3, an l-cysteic acid synthase homologue, suggested the single A domain in module 2 activates both l-Asp and l-cysteic acid to yield 1 and 2, respectively, although the substrate specificities of the A domains of NRPSs are usually strict. Biosynthetic mechanism of introduction of N-terminal Paa was also investigated. Recombinant Orf1 and Orf2 similar to subunits of pyruvate dehydrogenase complex catalyzed the conversion of phenylpyruvate into phenylacetyl-CoA together with dihydrolipoyl dehydrogenase whose encoding gene is located outside of the gene cluster. Moreover, we showed that phenylacetyl-CoA was directly condensed with l-Val, which was tethered to a peptidyl carrier protein, at the first condensation domain in the NRPS.
Formation of the bisulfite anion (HSO3 -, m/z 81) upon collision-induced dissociation of anions derived from organic sulfonic acids
Jariwala, Freneil B.,Wood, Ryan E.,Nishshanka, Upul,Attygalle, Athula B.
experimental part, p. 529 - 538 (2012/08/28)
In the negative-ion collision-induced dissociation mass spectra of most organic sulfonates, the base peak is observed at m/z 80 for the sulfur trioxide radical anion (SO3 -·). In contrast, the product-ion spectra of a few sulfonates, such as cysteic acid, aminomethanesulfonate, and 2-phenylethanesulfonate, show the base peak at m/z 81 for the bisulfite anion (HSO3 - ). An investigation with an extensive variety of sulfonates revealed that the presence of a hydrogen atom at the β-position relative to the sulfur atom is a prerequisite for the formation of the bisulfite anion. The formation of HSO3 - is highly favored when the atom at the β-position is nitrogen, or the leaving neutral species is a highly conjugated molecule such as styrene or acrylic acid. Deuterium-exchange experiments with aminomethanesulfonate demonstrated that the hydrogen for HSO3 - formation is transferred from the β-position. The presence of a peak at m/z 80 in the spectrum of 2-sulfoacetic acid, in contrast to a peak at m/z 81 in that of 3-sulfopropanoic acid, corroborated the proposed hydrogen transfer mechanism. For diacidic compounds, such as 4-sulfobutanoic acid and cysteic acid, the m/z 81 ion can be formed by an alternative mechanism, in which the negative charge of the carboxylate moiety attacks the α-carbon relative to the sulfur atom. Experiments conducted with deuterium-exchanged and deuterium-labeled analogs of sulfocarboxylic acids demonstrated that the formation of the bisulfite anion resulted either from a hydrogen transfer from the β-carbon, or from a direct attack by the carboxylate moiety on the α-carbon. Copyright
Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides
Kwan, Jason C.,Ratnayake, Ranjala,Abboud, Khalil A.,Paul, Valerie J.,Luesch, Hendrik
experimental part, p. 8012 - 8023 (2011/03/20)
Grassypeptolides A-C (1-3), a group of closely related bis-thiazoline containing cyclic depsipeptides, have been isolated from extracts of the marine cyanobacterium Lyngbya confervoides. Although structural differences between the analogues are minimal, comparison of the in vitro cytotoxicity of the series revealed a structure-activity relationship. When the ethyl substituent of 1 is changed to a methyl substituent in 2, activity is only slightly reduced (3-4-fold), whereas inversion of the Phe unit flanking the bis-thiazoline moiety results in 16-23-fold greater potency. We show that both 1 and 3 cause G1 phase cell cycle arrest at lower concentrations, followed at higher concentrations by G2/M phase arrest, and that these compounds bind Cu2+ and Zn 2+. The three-dimensional structure of 2 was determined by MS, NMR, and X-ray crystallography, and the structure of 3 was established by MS, NMR, and chemical degradation. The structure of 3 was explored by in silico molecular modeling, revealing subtle differences in overall conformation between 1 and 3. Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense.
