30801-99-1Relevant academic research and scientific papers
Chemoenzymatic Synthesis of Acyl Coenzyme A Substrates Enables in Situ Labeling of Small Molecules and Proteins
Agarwal, Vinayak,Diethelm, Stefan,Ray, Lauren,Garg, Neha,Awakawa, Takayoshi,Dorrestein, Pieter C.,Moore, Bradley S.
, p. 4452 - 4455 (2015)
A chemoenzymatic approach to generate fully functional acyl coenzyme A molecules that are then used as substrates to drive in situ acyl transfer reactions is described. Mass spectrometry based assays to verify the identity of acyl coenzyme A enzymatic products are also illustrated. The approach is responsive to a diverse array of carboxylic acids that can be elaborated to their corresponding coenzyme A thioesters, with potential applications in wide-ranging chemical biology studies that utilize acyl coenzyme A substrates.
Characterization and functional analysis of 4-coumarate:CoA ligase genes in mul-berry
Wang, Chuan-Hong,Yu, Jian,Cai, Yu-Xiang,Zhu, Pan-Pan,Liu, Chang-Ying,Zhao, Ai-Chun,Lü, Rui-Hua,Li, Meng-Jiao,Xu, Feng-Xiang,Yu, Mao-De
, (2016/06/08)
A small, multigene family encodes 4-coumarate:CoA ligases (4CLs) that catalyze the ligation of CoA to hydroxycinnamic acids, a branch point directing metabolites to flavonoid or monolignol pathways. In this study, we characterized four 4CL genes from M. n
Screening and Engineering the Synthetic Potential of Carboxylating Reductases from Central Metabolism and Polyketide Biosynthesis
Peter, Dominik M.,Schada Von Borzyskowski, Lennart,Kiefer, Patrick,Christen, Philipp,Vorholt, Julia A.,Erb, Tobias J.
supporting information, p. 13457 - 13461 (2015/11/09)
Carboxylating enoyl-thioester reductases (ECRs) are a recently discovered class of enzymes. They catalyze the highly efficient addition of CO2 to the double bond of α,β-unsaturated CoA-thioesters and serve two biological functions. In primary metabolism of many bacteria they produce ethylmalonyl-CoA during assimilation of the central metabolite acetyl-CoA. In secondary metabolism they provide distinct α-carboxyl-acyl-thioesters to vary the backbone of numerous polyketide natural products. Different ECRs were systematically assessed with a diverse library of potential substrates. We identified three active site residues that distinguish ECRs restricted to C4 and C5-enoyl-CoAs from highly promiscuous ECRs and successfully engineered a selected ECR as proof-of-principle. This study defines the molecular basis of ECR reactivity, allowing for predicting and manipulating a key reaction in natural product diversification.
Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds
Chang, Chenchen,Huang, Rong,Yan, Yan,Ma, Hongmin,Dai, Zheng,Zhang, Benying,Deng, Zixin,Liu, Wen,Qu, Xudong
supporting information, p. 4183 - 4190 (2015/04/14)
Selective modification of carbon scaffolds via biosynthetic engineering is important for polyketide structural diversification. Yet, this scope is currently restricted to simple aliphatic groups due to (1) limited variety of CoA-linked extender units, which lack aromatic structures and chemical reactivity, and (2) narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked extender units. In this report, we uncovered and characterized the first aromatic CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a deamination/reductive carboxylation strategy to convert phenylalanine into benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender unit synthesis. By characterization of its selection, we further validated that AT domains of splenocin, and antimycin polyketide synthases are able to select this extender unit to introduce the phenyl group into their dilactone scaffolds. The biosynthetic machinery involved in the formation of this extender unit is highly versatile and can be potentially tailored for tyrosine, histidine and aspartic acid. The disclosed aromatic extender unit, amino acid-oriented synthetic pathway, and aromatic-selective AT domains provides a systematic breakthrough toward current knowledge of polyketide extender unit formation and selection, and also opens a route for further engineering of polyketide carbon scaffolds using amino acids.
Multiplexing of combinatorial chemistry in antimycin biosynthesis: Expansion of molecular diversity and utility
Yan, Yan,Chen, Jing,Zhang, Lihan,Zheng, Qingfei,Han, Ying,Zhang, Hua,Zhang, Daozhong,Awakawa, Takayoshi,Abe, Ikuro,Liu, Wen
, p. 12308 - 12312 (2013/12/04)
Diversity-oriented biosynthesis of a library of antimycin-like compounds (380 altogether) was accomplished by using multiplex combinatorial biosynthesis. The core strategy depends on the use of combinatorial chemistry at different biosynthetic stages. This approach is applicable for the diversification of polyketides, nonribosomal peptides, and the hybrids that share a similar biosynthetic logic. Copyright
Establishing a toolkit for precursor-directed polyketide biosynthesis: Exploring substrate promiscuities of acid-CoA ligases
Go, Maybelle Kho,Chow, Jeng Yeong,Cheung, Vivian Wing Ngar,Lim, Yan Ping,Yew, Wen Shan
experimental part, p. 4568 - 4579 (2012/08/28)
Polyketides are chemically diverse and medicinally important biochemicals that are biosynthesized from acyl-CoA precursors by polyketide synthases. One of the limitations to combinatorial biosynthesis of polyketides has been the lack of a toolkit that describes the means of delivering novel acyl-CoA precursors necessary for polyketide biosynthesis. Using five acid-CoA ligases obtained from various plants and microorganisms, we biosynthesized an initial library of 79 acyl-CoA thioesters by screening each of the acid-CoA ligases against a library of 123 carboxylic acids. The library of acyl-CoA thioesters includes derivatives of cinnamyl-CoA, 3-phenylpropanoyl-CoA, benzoyl-CoA, phenylacetyl-CoA, malonyl-CoA, saturated and unsaturated aliphatic CoA thioesters, and bicyclic aromatic CoA thioesters. In our search for the biosynthetic routes of novel acyl-CoA precursors, we discovered two previously unreported malonyl-CoA derivatives (3-thiophenemalonyl-CoA and phenylmalonyl-CoA) that cannot be produced by canonical malonyl-CoA synthetases. This report highlights the utility and importance of determining substrate promiscuities beyond conventional substrate pools and describes novel enzymatic routes for the establishment of precursor-directed combinatorial polyketide biosynthesis. (Chemical Presented).
INDUCTION OF PHENYLPROPANOID PATHWAY ENZYMES IN ELICITOR-TREATED CULTURES OF CEPHALOCEREUS SENILIS
Pare, Paul W.,Mischke, Charles F.,Edwards, Robert,Dixon, Richard A.,Norman, Helen A.,Mabry, Tom J.
, p. 149 - 154 (2007/10/02)
Treatment of old-man-cactus (Cephalocereus senilis) suspension cultures with chitin elicits synthesis of an aurone phytoalexin, cephalocerone.Elicitor-induced de novo synthesis of cephalocerone was demonstrated by incubating elicited cactus cultures with phenylalanine; this resulted in the labelling of five induced phenolic compounds including cephalocerone.Increased extractable activities of the phenylpropanoid pathway enzymes phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS) and chalcone isomerase (CHI) accompanied the synthesis of cephalocerone.CHS and PAL, which are both involved in the biosynthesis of cephaloce rone, showed maximum activity at 12 and 24 hr post-elicitation, respectively.CHS and CHI activities catalysing the synthesis and subsequent isomerization of 2',4',6'-trihydroxychalcone were present in the cell cultures, consistent with the formation of cephalocerone via a chalcone with no B-ring substituents. Key Word Index - Cephalocereus senilis; Cactaceae; aurone; phytoalexin; enzyme induction; suspension culture; HPLC.
