In Silico Identification of Type III PKS Chalcone and Stilbene Synthase Homologs in Marine Photosynthetic Organisms

Marine microalgae are photosynthetic microorganisms at the base of the marine food webs. They are characterized by huge taxonomic and metabolic diversity and several species have been shown to have bioactivities useful for the treatment of human pathologies. However, the compounds and the metabolic pathways responsible for bioactive compound synthesis are often still unknown. In this study, we aimed at analysing the microalgal transcriptomes available in the Marine Microbial Eukaryotic Transcriptome Sequencing Project (MMETSP) database for an in silico search of polyketide synthase type III homologs and, in particular, chalcone synthase (CHS) and stilbene synthase (STS), which are often referred to as the CHS/STS family. These enzymes were selected because they are known to produce compounds with biological properties useful for human health, such as cancer chemopreventive, anti-inflammatory, antioxidant, anti-angiogenic, anti-viral and anti-diabetic. In addition, we also searched for 4-Coumarate: CoA ligase, an upstream enzyme in the synthesis of chalcones and stilbenes. This study reports for the first time the occurrence of these enzymes in specific microalgal taxa, confirming the importance for microalgae of these pathways and giving new insights into microalgal physiology and possible biotechnological applications for the production of bioactive compounds.

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Monogalactosyldiacylglycerol and Sulfolipid Synthesis in Microalgae

Marine Drugs ◽

10.3390/md18050237 ◽

2020 ◽

Vol 18 (5) ◽

pp. 237 ◽

Cited By ~ 5

Author(s):

Gennaro Riccio ◽

Daniele De Luca ◽

Chiara Lauritano

Keyword(s):

Metabolic Pathways ◽

Biological Properties ◽

Bioactive Lipids ◽

Metabolic Diversity ◽

Glutaminyl Cyclase ◽

Sequencing Project ◽

Bioactive Natural Products ◽

Anti Cancer ◽

Almost All ◽

First Time

Microalgae, due to their huge taxonomic and metabolic diversity, have been shown to be a valuable and eco-friendly source of bioactive natural products. The increasing number of genomic and transcriptomic data will give a great boost for the study of metabolic pathways involved in the synthesis of bioactive compounds. In this study, we analyzed the presence of the enzymes involved in the synthesis of monogalactosyldiacylglycerols (MGDGs) and sulfoquinovosyldiacylglycerols (SQDG). Both compounds have important biological properties. MGDGs present both anti-inflammatory and anti-cancer activities while SQDGs present immunostimulatory activities and inhibit the enzyme glutaminyl cyclase, which is involved in Alzheimer’s disease. The Ocean Global Atlas (OGA) database and the Marine Microbial Eukaryotic Transcriptome Sequencing Project (MMETSP) were used to search MGDG synthase (MGD), UDP-sulfoquinovose synthase (SQD1), and sulfoquinovosyltransferase (SQD2) sequences along microalgal taxa. In silico 3D prediction analyses for the three enzymes were performed by Phyre2 server, while binding site predictions were performed by the COACH server. The analyzed enzymes are distributed across different taxa, which confirms the importance for microalgae of these two pathways for thylakoid physiology. MGD genes have been found across almost all analyzed taxa and can be separated in two different groups, similarly to terrestrial plant MGD. SQD1 and SQD2 genes are widely distributed along the analyzed taxa in a similar way to MGD genes with some exceptions. For Pinguiophyceae, Raphidophyceae, and Synurophyceae, only sequences coding for MGDG were found. On the contrary, sequences assigned to Ciliophora and Eustigmatophyceae were exclusively corresponding to SQD1 and SQD2. This study reports, for the first time, the presence/absence of these enzymes in available microalgal transcriptomes, which gives new insights on microalgal physiology and possible biotechnological applications for the production of bioactive lipids.

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Molecular analysis of a type III polyketide synthase gene in Fallopia multiflora

Biologia ◽

10.2478/s11756-010-0113-8 ◽

2010 ◽

Vol 65 (6) ◽

Cited By ~ 6

Author(s):

Shu-Jing Sheng ◽

Zhong-Yu Liu ◽

Wei Zhao ◽

Li Shao ◽

Shu-Jin Zhao

Keyword(s):

Polyketide Synthase ◽

Stilbene Synthase ◽

Northern Blotting ◽

Amino Acid Residues ◽

Type Iii Polyketide Synthase ◽

Reading Frame ◽

Type Iii ◽

Close Relationship ◽

Polyketide Synthase Gene ◽

Cloned Gene

AbstractA type III polyketide synthase (PKS) cDNA and the corresponding gene (FmPKS) were isolated from the rhizomes of Fallopia multiflora (Thunb.) (Polygonaceae). The full-length FmPKS cDNA was 1,228 bp, containing an open reading frame of 1,137 bp encoding a 378 amino acid residues long protein. The coding sequence of the gene was interrupted by three introns, a different gene structure from most of the type III PKS genes studied so far containing only one intron at a conserved site, except for the recently cloned gene PcPKS2 from Polygonum cuspidatum. Phylogenetic analysis revealed that it shares a close relationship with Rheum tataricum stilbene synthase and formes a group with functionally diverse chalcone synthase-like enzymes. Southern blotting showed that there are three to four copies of the FmPKS gene in the genome. The expression pattern of the FmPKS transcript was determined by Northern blotting and high expression levels were detected in rhizomes and old stems, while the lowest levels were found in old leaves, a pattern that strongly correlates with the accumulation of the major bioactive principles called 2,3,5,4’-tetra-hydroxy-stilbene-2-O-β-D-glucoside, suggesting that FmPKS might play an important role in its biosynthesis.

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Neuropharmacological Screening of Chiral and Non-chiral Phthalimide- Containing Compounds in Mice: in vivo and in silico Experiments

Medicinal Chemistry ◽

10.2174/1573406414666180525082038 ◽

2019 ◽

Vol 15 (1) ◽

pp. 102-118 ◽

Cited By ~ 1

Author(s):

Carolina Campos-Rodríguez ◽

José G. Trujillo-Ferrara ◽

Ameyali Alvarez-Guerra ◽

Irán M. Cumbres Vargas ◽

Roberto I. Cuevas-Hernández ◽

...

Keyword(s):

Locomotor Activity ◽

In Silico ◽

Biological Properties ◽

Chiral Molecules ◽

Chiral Compounds ◽

Plus Maze ◽

In Silico Studies ◽

The Central Nervous System

Background: Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. Objective: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. Method: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). Results: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. Conclusion: The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

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Discovery of anti-infective adipostatins through bioactivity-guided isolation and heterologous expression of a type III polyketide synthase

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.104925 ◽

2021 ◽

pp. 104925

Author(s):

Lukuan Hou ◽

Ying Li ◽

Qihao Wu ◽

Miyang Li ◽

Ethan A. Older ◽

...

Keyword(s):

Heterologous Expression ◽

Polyketide Synthase ◽

Type Iii Polyketide Synthase ◽

Type Iii

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Bioactive Compounds in Salicornia patula Duval-Jouve: A Mediterranean Edible Euhalophyte

Foods ◽

10.3390/foods10020410 ◽

2021 ◽

Vol 10 (2) ◽

pp. 410

Author(s):

Irene Sánchez-Gavilán ◽

Esteban Ramírez ◽

Vicenta de la Fuente

Keyword(s):

Fatty Acids ◽

Bioactive Compounds ◽

Mediterranean Area ◽

Biological Properties ◽

Total Phenolic ◽

Tinto River ◽

New Findings ◽

High Concentrations ◽

Salicornia Patula ◽

First Time

Many halophytes have great nutritional and functional potential, providing chemical compounds with biological properties. Salicornia patula Duval-Jouve is a common euhalophyte from saline Mediterranean territories (Spain, Portugal, France, and Italy). In the present work we quantified for the first time the bioactive compounds in S. patula (total phenolic compounds and fatty acids), from Iberian Peninsula localities: littoral-coastal Tinto River basin areas (southwest Spain, the Huelva province), and mainland continental territories (northwest and central Spain, the Valladolid and Madrid provinces). Five phenolic acids including caffeic, coumaric, veratric, salicylic, and transcinnamic have been found with differences between mainland and coastal saltmarshes. S. patula contain four flavonoids: quercetin-3-O-rutinoside, kaempferol/luteolin, apigenin 7-glucoside, and pelargonidin-3-O-rutinoside. These last two glycosylated compounds are described for the first time in this genus of Chenopodiaceae. The fatty acid profile described in S. patula stems contains palmitic, oleic, and linoleic acids in high concentrations, while stearic and long-chain fatty acids were detected in low amounts. These new findings confirm that S. patula is a valuable source of bioactive compounds from Mediterranean area.

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Biosynthesis of resveratrol derivatives and evaluation of their anti-inflammatory activity

Applied Biological Chemistry ◽

10.1186/s13765-021-00607-4 ◽

2021 ◽

Vol 64 (1) ◽

Author(s):

Yoojin Chong ◽

Hye Lim Lee ◽

Jihyeon Song ◽

Youngshim Lee ◽

Bong-Gyu Kim ◽

...

Keyword(s):

Biological Activities ◽

Stilbene Synthase ◽

Inflammatory Activity ◽

E Coli ◽

Prephenate Dehydrogenase ◽

Coa Ligase ◽

Final Yield ◽

Resveratrol Derivatives ◽

Anti Inflammatory ◽

Tyrosine Biosynthesis

AbstractResveratrol is a typical plant phenolic compound whose derivatives are synthesized through hydroxylation, O-methylation, prenylation, and oligomerization. Resveratrol and its derivatives exhibit anti-neurodegenerative, anti-rheumatoid, and anti-inflammatory effects. Owing to the diverse biological activities of these compounds and their importance in human health, this study attempted to synthesize five resveratrol derivatives (isorhapontigenin, pterostilbene, 4-methoxyresveratrol, piceatannol, and rhapontigenin) using Escherichia coli. Two-culture system was used to improve the final yield of resveratrol derivatives. Resveratrol was synthesized in the first E. coli cell that harbored genes for resveratrol biosynthesis including TAL (tyrosine ammonia lyase), 4CL (4-coumaroyl CoA ligase), STS (stilbene synthase) and genes for tyrosine biosynthesis such as aroG (deoxyphosphoheptonate aldolase) and tyrA (prephenate dehydrogenase). Thereafter, culture filtrate from the first cell was used for the modification reaction carried out using the second E. coli harboring hydroxylase and/or O-methyltransferase. Approximately, 89.8 mg/L of resveratrol was synthesized and using the same, five derivatives were prepared with a conversion rate of 88.2% to 22.9%. Using these synthesized resveratrol derivatives, we evaluated their anti-inflammatory activity. 4-Methoxyresveratrol, pterostilbene and isorhapontigenin showed the anti-inflammatory effects without any toxicity. In addition, pterostilbene exhibited the enhanced anti-inflammatory effects for macrophages compared to resveratrol.

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A Fine Balancing Act of Type III Polyketide Synthase

Chemistry & Biology ◽

10.1016/j.chembiol.2004.09.001 ◽

2004 ◽

Vol 11 (9) ◽

pp. 1177-1178 ◽

Cited By ~ 1

Author(s):

Shiou-Chuan Tsai

Keyword(s):

Polyketide Synthase ◽

Type Iii Polyketide Synthase ◽

Type Iii

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Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase

Nature Chemical Biology ◽

10.1038/nchembio811 ◽

2006 ◽

Vol 2 (9) ◽

pp. 494-502 ◽

Cited By ~ 86

Author(s):

Michael B Austin ◽

Tamao Saito ◽

Marianne E Bowman ◽

Stephen Haydock ◽

Atsushi Kato ◽

...

Keyword(s):

Fatty Acid ◽

Dictyostelium Discoideum ◽

Polyketide Synthase ◽

Type I ◽

Type Iii Polyketide Synthase ◽

Type Iii ◽

Hybrid Type ◽

Acid Type ◽

Fatty Acid Type

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In silico identification of Capsicum type III polyketide synthase genes and expression patterns in Capsicum annuum

Open Life Sciences ◽

10.1515/biol-2020-0077 ◽

2020 ◽

Vol 15 (1) ◽

pp. 753-762

Author(s):

Delong Kan ◽

Di Zhao ◽

Pengfei Duan

Keyword(s):

Molecular Mechanisms ◽

Polyketide Synthase ◽

Expression Patterns ◽

Class Ii ◽

Chili Pepper ◽

Type Iii Polyketide Synthase ◽

Type Iii ◽

Genes Encoding ◽

Duplication Events ◽

Pepper Leaves

AbstractStudies have shown that abundant and various flavonoids accumulate in chili pepper (Capsicum), but there are few reports on the genes that govern chili pepper flavonoid biosynthesis. Here, we report the comprehensive identification of genes encoding type III polyketide synthase (PKS), an important enzyme catalyzing the generation of flavonoid backbones. In total, 13, 14 and 13 type III PKS genes were identified in each genome of C. annuum, C. chinense and C. baccatum, respectively. The phylogeny topology of Capsicum PKSs is similar to those in other plants, as it showed two classes of genes. Within each class, clades can be further identified. Class II genes likely encode chalcone synthase (CHS) as they are placed together with the Arabidopsis CHS gene, which experienced extensive expansions in the genomes of Capsicum. Interestingly, 8 of the 11 Class II genes form three clusters in the genome of C. annuum, which is likely the result of tandem duplication events. Four genes are not expressed in the tissues of C. annuum, three of which are located in the clusters, indicating that a portion of genes was pseudogenized after tandem duplications. Expression of two Class I genes was complementary to each other, and all the genes in Class II were not expressed in roots of C. annuum. Two Class II genes (CA00g90790 and CA05g17060) showed upregulated expression as the chili pepper leaves matured, and two Class II genes (CA05g17060 and CA12g20070) showed downregulated expression with the maturation of fruits, consistent with flavonoid accumulation trends in chili pepper as reported previously. The identified genes, sequences, phylogeny and expression information collected in this article lay the groundwork for future studies on the molecular mechanisms of chili pepper flavonoid metabolism.

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