1504-56-9Relevant articles and documents
Engineering monolignol 4-O-methyltransferases to modulate lignin biosynthesis
Bhuiya, Mohammad-Wadud,Liu, Chang-Jun
, p. 277 - 285 (2010)
Lignin is a complex polymer derived from the oxidative coupling of three classical monolignols. Lignin precursors are methylated exclusively at the meta-positions (i.e. 3/5-OH) of their phenyl rings by native O-methyltransferases, and are precluded from substitution of the para-hydroxyl (4-OH) position. Ostensibly, the para-hydroxyls of phenolics are critically important for oxidative coupling of phenoxy radicals to form polymers. Therefore, creating a 4-O-methyltransferase to substitute the para-hydroxyl of monolignols might well interfere with the synthesis of lignin. The phylogeny of plant phenolic O-methyltransferases points to the existence of a batch of evolutionarily plastic amino acid residues. Following one amino acid at a time path of directed evolution, and using the strategy of structure-based iterative site-saturation mutagenesis, we created a novel monolignol 4-O-methyltransferase from the enzyme responsible for methylating phenylpropenes. We show that two plastic residues in the active site of the parental enzyme are vital in dominating substrate discrimination. Mutations at either one of these separate the evolutionarily tightly linked properties of substrate specificity and regioselective methylation of native O-methyltransferase, thereby conferring the ability for para-methylation of the lignin monomeric precursors, primarily monolignols. Beneficial mutations at both sites have an additive effect. By further optimizing enzyme activity, we generated a triple mutant variant that may structurally constitute a novel phenolic substrate binding pocket, leading to its high binding affinity and catalytic efficiency on monolignols. The 4-O-methoxylation of monolignol efficiently impairs oxidative radical coupling in vitro, highlighting the potential for applying this novel enzyme in managing lignin polymerization in planta.
Synthesis, antiepileptic effects, and structure-activity relationships of α-asarone derivatives: In vitro and in vivo neuroprotective effect of selected derivatives
Zhang, Jian,Mu, Keman,Yang, Peng,Feng, Xinqian,Zhang, Di,Fan, Xiangyu,Wang, Qiantao,Mao, Shengjun
, (2021/08/03)
In the present study, we compared the antiepileptic effects of α-asarone derivatives to explore their structure-activity relationships using the PTZ-induced seizure model. Our research revealed that electron-donating methoxy groups in the 3,4,5-position on phenyl ring increased antiepileptic potency but the placement of other groups at different positions decreased activity. Besides, in allyl moiety, the optimal activity was reached with either an allyl or a 1-butenyl group in conjugation with the benzene ring. The compounds 5 and 19 exerted better neuroprotective effects against epilepsy in vitro (cell) and in vivo (mouse) models. This study provides valuable data for further exploration and application of these compounds as potential anti-seizure medicines.
Microbial Production of Natural and Unnatural Monolignols with Escherichia coli
Aschenbrenner, Jennifer,Marx, Patrick,Pietruszka, J?rg,Marienhagen, Jan
, p. 949 - 954 (2019/02/26)
Phenylpropanoids and phenylpropanoid-derived plant polyphenols find numerous applications in the food and pharmaceutical industries. In recent years, several microbial platform organisms have been engineered towards producing such compounds. However, for the most part, microbial (poly)phenol production is inspired by nature, so naturally occurring compounds have predominantly been produced to date. Here we have taken advantage of the promiscuity of the enzymes involved in phenylpropanoid synthesis and exploited the versatility of an engineered Escherichia coli strain harboring a synthetic monolignol pathway to convert supplemented natural and unnatural phenylpropenoic acids into their corresponding monolignols. The performed biotransformations showed that this strain is able to catalyze the stepwise reduction of chemically interesting unnatural phenylpropenoic acids such as 3,4,5-trimethoxycinnamic acid, 5-bromoferulic acid, 2-nitroferulic acid, and a “bicyclic” p-coumaric acid derivative, in addition to six naturally occurring phenylpropenoic acids.
Copper Hydride Catalyzed Reductive Claisen Rearrangements
Wong, Kong Ching,Ng, Elvis,Wong, Wing-Tak,Chiu, Pauline
supporting information, p. 3709 - 3712 (2016/03/08)
An efficient reductive Claisen rearrangement, catalyzed by in situ generated copper hydride and stoichiometric in diethoxymethylsilane, has been developed. Yields of up to 95 ;% with good to excellent diastereoselectivities were observed in this reaction. Mechanistic studies showed that the stereospecific rearrangement proceeded via a chair transition state of (E)-silyl ketene acetals as intermediates and not via the copper enolates.
