112083-63-3Relevant articles and documents
Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids
Touchette, Megan H.,Bommineni, Gopal R.,Delle Bovi, Richard J.,Gadbery, John E.,Nicora, Carrie D.,Shukla, Anil K.,Kyle, Jennifer E.,Metz, Thomas O.,Martin, Dwight W.,Sampson, Nicole S.,Miller, W. Todd,Tonge, Peter J.,Seeliger, Jessica C.
, p. 5457 - 5468 (2015)
Although they are classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters known as dimycocerosates (DIMs) are significantly attenuated in model infections. The resultant interest in the biosynthetic pathway of these unusual virulence factors has led to the elucidation of many of the steps leading to the final esterification of the alkyl β-diol, phthiocerol, with branched-chain fatty acids known as mycocerosates. PapA5 is an acyltransferase implicated in these final reactions. Here, we show that PapA5 is indeed the terminal enzyme in DIM biosynthesis by demonstrating its dual esterification activity and chain-length preference using synthetic alkyl β-diol substrate analogues. By applying these analogues to a series of PapA5 mutants, we also revise a model for the substrate binding within PapA5. Finally, we demonstrate that the Mtb Ser/Thr kinases PknB and PknE modify PapA5 on three overlapping Thr residues and that a fourth Thr is unique to PknE phosphorylation. These results clarify the DIM biosynthetic pathway and indicate post-translational modifications that warrant further elucidation for their roles in the regulation of DIM biosynthesis.
Total synthesis of neopeltolide and analogs
Cui, Yubo,Tu, Wangyang,Floreancig, Paul E.
, p. 4867 - 4873 (2010)
Neopeltolide, a potent cytotoxin from a Carribean sponge, was synthesized through a brief sequence that highlights the use of ethers as oxocarbenium ion precursors. Other key steps include an acid-mediated etherification and sequence that features a Sonogashira reaction, an intramolecular alkyne hydrosilylation reaction, and a Tamao oxidation. The alkene that is required for the oxidative cyclization can be hydrogenated to provide access to the natural product or an epimer, or can be epoxidized or dihydroxylated to form polar analogs.
Study of Class i and Class III Polyhydroxyalkanoate (PHA) Synthases with Substrates Containing a Modified Side Chain
Jia, Kaimin,Cao, Ruikai,Hua, Duy H.,Li, Ping
, p. 1477 - 1485 (2016/05/09)
Polyhydroxyalkanoates (PHAs) are carbon and energy storage polymers produced by a variety of microbial organisms under nutrient-limited conditions. They have been considered as an environmentally friendly alternative to oil-based plastics due to their renewability, versatility, and biodegradability. PHA synthase (PhaC) plays a central role in PHA biosynthesis, in which its activity and substrate specificity are major factors in determining the productivity and properties of the produced polymers. However, the effects of modifying the substrate side chain are not well understood because of the difficulty to accessing the desired analogues. In this report, a series of 3-(R)-hydroxyacyl coenzyme A (HACoA) analogues were synthesized and tested with class I synthases from Chromobacterium sp. USM2 (PhaCCs and A479S-PhaCCs) and Caulobacter crescentus (PhaCCc) as well as class III synthase from Allochromatium vinosum (PhaECAv). It was found that, while different PHA synthases displayed distinct preference with regard to the length of the alkyl side chains, they could withstand moderate side chain modifications such as terminal unsaturated bonds and the azide group. Specifically, the specific activity of PhaCCs toward propynyl analogue (HHxyCoA) was only 5-fold less than that toward the classical substrate HBCoA. The catalytic efficiency (kcat/Km) of PhaECAv toward azide analogue (HABCoA) was determined to be 2.86 × 105 M-1 s-1, which was 6.2% of the value of HBCoA (4.62 × 106 M-1 s-1) measured in the presence of bovine serum albumin (BSA). These side chain modifications may be employed to introduce new material functions to PHAs as well as to study PHA biogenesis via click-chemistry, in which the latter remains unknown and is important for metabolic engineering to produce PHAs economically.
Synthesis of ethyl (R)-4-cyano-3-hydroxybutyrate in high concentration using a novel halohydrin dehalogenase HHDH-PL from Parvibaculum lavamentivorans DS-1
Wan, Nan-Wei,Liu, Zhi-Qiang,Huang, Kai,Shen, Zhen-Yang,Xue, Feng,Zheng, Yu-Guo,Shen, Yin-Chu
, p. 64027 - 64031 (2015/02/19)
We identified and characterized a novel halohydrin dehalogenase HHDH-PL from Parvibaculum lavamentivorans DS-1. Study of substrate specificity indicated that HHDH-PL possessed a high activity toward ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE). After optimizations of the pH and temperature, whole cell catalysis of HHDH-PL was applied to the synthesis of ethyl (R)-4-cyano-3-hydroxybutyrate (HN) at 200 g L-1 of (S)-CHBE, which gave 95% conversion and 85% yield in 14 h.
