Synthetic analog of anticancer drug daunorubicin from daunorubicinone using one-pot enzymatic UDP-recycling glycosylation

Chu, Luan Luong; Pandey, Ramesh Prasad; Shin, Ju Yong; Jung, Hye Jin; Sohng, Jae Kyung

doi:10.1016/j.molcatb.2015.11.020

Cited by 17 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…). YjiC is a typical GT‐B fold enzyme possessing two separate domains ( N ‐terminal acceptor binding domain and the C ‐terminal sugar donor binding domain) and exhibiting the promiscuous capacity to catalyse the glycosylation of other compounds, such as geldanamycin, resveratrol and daunomycin (Wu et al ., ; Pandey et al ., ,; Chu et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Phylogeny‐guided characterization of glycosyltransferases for epothilone glycosylation

Zhang

Zheng

et al. 2019

Microbial Biotechnology

View full text Add to dashboard Cite

Summary Glycosylation of natural products can influence their pharmacological properties, and efficient glycosyltransferases (GTs) are critical for this purpose. The polyketide epothilones are potent anti‐tumour compounds, and YjiC is the only reported GT for the glycosylation of epothilone. In this study, we phylogenetically analysed 8261 GTs deposited in CAZy database and revealed that YjiC locates in a subbranch of the Macrolide I group, forming the YjiC‐subbranch with 160 GT sequences. We demonstrated that the YjiC‐subbranch GTs are normally efficient in epothilone glycosylation, but some showed low glycosylation activities. Sequence alignment of YjiC‐subbranch showed that the 66th and 77th amino acid residues, which were close to the catalytic cavity in molecular docking model, were conserved in five high‐active GTs (Q66 and P77) but changed in two low‐efficient GTs. Site‐directed residues swapping at the two positions in the two low‐active GTs (BssGT and BamGT) and the high‐active GT BsGT‐1 demonstrated that the two amino acid residues played an important role in the catalytic efficiency of epothilone glycosylation. This study highlights that the potent GTs for appointed compounds are phylogenetically grouped with conserved residues for the catalytic efficiency.

show abstract

Section: Introductionmentioning

confidence: 97%

Phylogeny‐guided characterization of glycosyltransferases for epothilone glycosylation

Zhang

Zheng

et al. 2019

Microbial Biotechnology

View full text Add to dashboard Cite

show abstract

“…First, umbelliferone was oxidized by CYP450 BM3 from B. megaterium and its variant M13 to produce metabolite esculetin. Second, a flexible glycosyltransferase YjiC from B. licheniformis capable of accepting various small molecules such as chalcone [24, 25], flavonoids [26], stilbene [27], and anthracycline antibiotic were used for efficient glycosylation of umbelliferone to produce skimmin [28]. Finally, we extended acceptor substrate of SaOMT2 from S. avermitilis [29] to produce herniarin.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of umbelliferone derivatives in Escherichia coli and their biological activities

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundUmbelliferone, also known as 7-hydroxycoumarin, is a phenolic metabolite found in many familiar plants. Its derivatives have been shown to have various pharmacological and chemo-preventive effects on human health. A uridine diphosphate glycosyltransferase YjiC from Bacillus licheniformis DSM 13, a cytochrome P450BM3 (CYP450 BM3) variant namely mutant 13 (M13) from Bacillus megaterium, and an O-methyltransferase from Streptomyces avermitilis (SaOMT2) were used for modifications of umbelliferone.ResultsThree umbelliferone derivatives (esculetin, skimmin, and herniarin) were generated through enzymatic and whole cell catalysis. To improve the efficiencies of biotransformation, different media, incubation time and concentration of substrate were optimized and the production was scaled up using a 3-L fermentor. The maximum yields of esculetin, skimmin, and herniarin were 337.10 μM (67.62%), 995.43 μM (99.54%), and 37.13 μM (37.13%), respectively. The water solubility of esculetin and skimmin were 1.28-folds and 3.98-folds as high as umbelliferone, respectively, whereas herniarin was 1.89-folds less soluble than umbelliferone. Moreover, the antibacterial and anticancer activities of herniarin showed higher than umbelliferone, esculetin and skimmin.ConclusionsThis study proves that both native and engineered enzymes could be employed for the production of precious compounds via whole cell biocatalysis. We successfully produced three molecules herniarin, esculetin and skimmin in practical amounts and their antibacterial and anticancer properties were accessed. One of the newly synthesized molecules the present research suggests that the combinatorial biosynthesis of different biosynthetic enzymes could rapidly promote to a novel secondary metabolite.Electronic supplementary materialThe online version of this article (doi:10.1186/s13036-017-0056-5) contains supplementary material, which is available to authorized users.

show abstract

“…Enzymatic glycosylations were performed on various acceptors (e.g., quercetin, resveratrol, phloretin, stevioside, curcumin) using sugar donor regeneration. ,− However, final product concentrations, after some optimizations, were typically still in the low millimolar range, reflecting limitations on acceptor substrate solubility. Therefore, unlike oligosaccharide synthesis, these reactions can hardly challenge the performance of the regeneration systems used.…”

Section: Glycosyltransferase-catalyzed Synthesis: Systems and Paramet...mentioning

confidence: 99%

Leloir Glycosyltransferases as Biocatalysts for Chemical Production

2018

View full text Add to dashboard Cite

Glycosylation is a chemical transformation that is centrally important in all glycoscience and related technologies. Catalysts offering good control over reactivity and selectivity in synthetic glycosylations are much sought. The enzymes responsible for glycosylations in natural biosynthesis are sugar-nucleotide-dependent (Leloir) glycosyltransferases. Discovery-oriented synthesis and pilot batch production of oligosaccharides and glycosylated natural products have previously relied on Leloir glycosyltransferases. However, despite their perceived synthetic utility, Leloir glycosyltransferases are yet to see widespread application in industrial biocatalysis. Here we show progress and limitations in the development of Leloir glycosyltransferases into robust biocatalytic systems for use in glycosylations for chemical production. Obtaining highly active and stable (whole-cell) catalysts that can promote the desired glycosylation(s) coupled to an in situ sugar nucleotide supply remains a difficult problem. Optimizing glycosyltransferase cascade reactions for high process efficiency is another. Glycosylations of some natural products (e.g., flavonoids, terpenoids) involve acceptor substrate solubility as a special challenge for biocatalytic process design. Strategies to overcome these problems are illustrated from examples of integrated biocatalytic process development with this class of enzymes.

show abstract

Synthetic analog of anticancer drug daunorubicin from daunorubicinone using one-pot enzymatic UDP-recycling glycosylation

Cited by 17 publications

References 36 publications

Phylogeny‐guided characterization of glycosyltransferases for epothilone glycosylation

Phylogeny‐guided characterization of glycosyltransferases for epothilone glycosylation

Synthesis of umbelliferone derivatives in Escherichia coli and their biological activities

Leloir Glycosyltransferases as Biocatalysts for Chemical Production

Contact Info

Product

Resources

About