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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 19221

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Dr. Yongjun Wei

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School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
Interests: plant natural products; yeast; metabolic engineering; synthetic biology; environmental microbiota; gut microbiota; precise modulation
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Lingbo Qu

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College of Chemistry, Institute of Analytical Chemistry for Life Science, Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou University, Zhengzhou, China
Interests: traditional medicinal plants; synthetic biology; chemical biology; food nutrition; pharmaceutical molecules

Prof. Dr. Xiao-Jun Ji

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Guest Editor

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, China
Interests: metabolic engineering; synthetic biology; oleaginous yeast; Yarrowia lipolytica; oleochemicals; terpenoids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plants and microorganisms, especially medicinal herbs, harbor diverse natural products. Among them, many are bioactive molecules, which have potential pharmaceutical or health applications. However, the compositions of these bioactive molecules in plants or microorganisms are usually low. The development of omics technologies and synthetic biology provide opportunities to produce bioactive molecules using metabolically engineered plants or microorganisms. Artemisinin, rare ginsenosides, and several other natural products have been produced on a large-scale. To further apply natural products, using cutting-edge synthetic biology and engineering biology technologies in plants and microorganisms is of great interest.

Dr. Yongjun Wei
Prof. Dr. Lingbo Qu
Prof. Dr. Xiao-Jun Ji
Guest Editors

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Keywords

natural products
bioactive molecules
medicinal herbs
metabolic engineering
microbial cell factories
synthetic biology
natural product biosynthetic pathway
omics technologies

Published Papers (9 papers)

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Research

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20 pages, 5800 KiB

Open AccessArticle

Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism

by Kang-Xi Zhang, Yue Zhu, Shu-Xia Song, Qing-Yun Bu, Xiao-Yan You, Hong Zou and Guo-Ping Zhao

Molecules 2024, 29(5), 1108; https://doi.org/10.3390/molecules29051108 - 01 Mar 2024

Viewed by 654

Abstract

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid β-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and β-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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21 pages, 5671 KiB

Open AccessArticle

Discovery of the Active Compounds of the Ethyl Acetate Extract Site of Ardisia japonica (Thunb.) Blume for the Treatment of Acute Lung Injury

by Shuding Sun, Xuefang Liu, Di Zhao, Lishi Zheng, Xiaoxiao Han, Yange Tian and Suxiang Feng

Molecules 2024, 29(4), 770; https://doi.org/10.3390/molecules29040770 - 07 Feb 2024

Viewed by 511

Abstract

The objective of this study was to identify and evaluate the pharmacodynamic constituents of Ardisiae Japonicae Herba (AJH) for the treatment of acute lung injury (ALI). To fully analyze the chemical contents of various extraction solvents (petroleum ether site (PE), ethyl acetate site (EA), n-butanol site (NB), and water site (WS)) of AJH, the UPLC–Orbitrap Fusion–MS technique was employed. Subsequently, the anti-inflammatory properties of the four extracted components of AJH were assessed using the lipopolysaccharide (LPS)-induced MH-S cellular inflammation model. The parts that exhibited anti-inflammatory activity were identified. Additionally, a technique was developed to measure the levels of specific chemical constituents in the anti-inflammatory components of AJH. The correlation between the “anti-inflammatory activity” and the constituents was analyzed, enabling the identification of a group of pharmacodynamic components with anti-inflammatory properties. ALI model rats were created using the tracheal drip LPS technique. The pharmacodynamic indices were evaluated for the anti-inflammatory active portions of AJH. The research revealed that the PE, EA, NB, and WS extracts of AJH included 215, 289, 128, and 69 unique chemical components, respectively. Additionally, 528 chemical components were discovered after removing duplicate values from the data. The EA exhibited significant anti-inflammatory activity in the cellular assay. A further analysis was conducted to determine the correlation between anti-inflammatory activity and components. Seventeen components, such as caryophyllene oxide, bergenin, and gallic acid, were identified as potential pharmacodynamic components with anti-inflammatory activity. The pharmacodynamic findings demonstrated that the intermediate and high doses of the EA extract from AJH exhibited a more pronounced effect in enhancing lung function, blood counts, and lung histology in a way that depended on the dosage. To summarize, when considering the findings from the previous study on the chemical properties of AJH, it was determined that the EA contained a group of 13 constituents that primarily contributed to its pharmacodynamic effects against ALI. The constituents include bergenin, quercetin, epigallocatechingallate, and others. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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22 pages, 3208 KiB

Open AccessArticle

Effect of Nano-Selenium on Nutritional Quality of Cowpea and Response of ABCC Transporter Family

by Li Li, Yuzhou Xiong, Yuan Wang, Shuai Wu, Chunmei Xiao, Shiyan Wang, Shuiyuan Cheng and Hua Cheng

Molecules 2023, 28(3), 1398; https://doi.org/10.3390/molecules28031398 - 01 Feb 2023

Cited by 5 | Viewed by 1416

Abstract

It is an important way for healthy Selenium (Se) supplement to transform exogenous Se into organic Se through crops. In the present study, Vigna unguiculata was selected as a test material and sprayed with biological nano selenium (SeNPs) and Na₂SeO₃, and its nutrient composition, antioxidant capacity, total Se and organic Se content were determined, respectively. Further, the response of ABC transporter family members in cowpea to different exogenous Se treatments was analyzed by transcriptome sequencing combined with different Se forms. The results show that the soluble protein content of cowpea increased after twice Se treatment. SeNPs treatment increased the content of cellulose in cowpea pods. Na₂SeO₃ treatment increased the content of vitamin C (Vc) in cowpea pods. Se treatments could significantly increase the activities of Peroxidase (POD), polyphenol oxidase (PPO) and catalase (CAT) in cowpea pods and effectively maintain the activity of Superoxide dismutase (SOD). SeNPs can reduce the content of malondialdehyde (MDA) in pods. After Se treatment, cowpea pods showed a dose-effect relationship on the absorption and accumulation of total Se, and Na₂SeO₃ treatment had a better effect on the increase of total Se content in cowpea pods. After treatment with SeNPs and Na₂SeO₃, the Se species detected in cowpea pods was mainly SeMet, followed by MeSeCys. Inorganic Se can only be detected in the high concentration treatment group. Analysis of transcriptome data of cowpea treated with Se showed that ABC transporters could play an active role in response to Se stress and Se absorption, among which ABCB, ABCC and ABCG subfamilies played a major role in Se absorption and transportation in cowpea. Further analysis by weighted gene co-expression network analysis (WGCNA) showed that the content of organic Se in cowpea treated with high concentration of SeNPs was significantly and positively correlated with the expression level of three transporters ABCC11, ABCC13 and ABCC10, which means that the ABCC subfamily may be more involved in the transmembrane transport of organic Se in cells. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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14 pages, 2003 KiB

Open AccessArticle

Antibacterial Activity of Syzygium aromaticum (Clove) Bud Oil and Its Interaction with Imipenem in Controlling Wound Infections in Rats Caused by Methicillin-Resistant Staphylococcus aureus

by Abdulaziz Khaleef Alanazi, Mohammed Hussein Alqasmi, Mohammed Alrouji, Fahd A. Kuriri, Yasir Almuhanna, Babu Joseph and Mohammed Asad

Molecules 2022, 27(23), 8551; https://doi.org/10.3390/molecules27238551 - 05 Dec 2022

Cited by 13 | Viewed by 3608

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of infection worldwide. Clove oil’s ability to inhibit the growth of MRSA was studied through in vitro and in vivo studies. The phytochemical components of clove oil were determined through gas chromatography-mass spectrometry (GC-MS) analysis. The antibacterial effects of clove oil and its interaction with imipenem were determined by studying MIC, MBC, and FIC indices in vitro. The in vivo wound-healing effect of the clove oil and infection control were determined using excision wound model rats. The GC-MS analysis of clove oil revealed the presence of 16 volatile compounds. Clove oil showed a good antibacterial effect in vitro but no interaction was observed with imipenem. Clove bud oil alone or in combination with imipenem healed wounds faster and reduced the microbial load in wounds. The findings of this study confirmed the antibacterial activity of clove oil in vitro and in vivo and demonstrated its interaction with imipenem. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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11 pages, 3061 KiB

Open AccessArticle

Lanostane Triterpenoids and Ergostane Steroids from Ganoderma luteomarginatum and Their Cytotoxicity

by Qingyun Ma, Shuangshuang Zhang, Li Yang, Qingyi Xie, Haofu Dai, Zhifang Yu and Youxing Zhao

Molecules 2022, 27(20), 6989; https://doi.org/10.3390/molecules27206989 - 18 Oct 2022

Cited by 4 | Viewed by 1500

Abstract

Macrofungus Ganoderma luteomarginatum is one of the main species of Ganoderma fungi distributed in Hainan province of China, the fruiting bodies of which have been widely used in folk as a healthy food to prevent tumors. To explore the potential cytotoxic constituents from G. luteomarginatum, the phytochemical investigation on the ethyl acetate soluble fraction of 95% ethanolic extract from the fruiting bodies of this fungus led to the isolation of twenty-six lanostane triterpenoids (1–26), including three undescribed ones (1–3), together with eight ergostane steroids (27–34). The structures of three new lanostane triterpenoids were elucidated as lanosta-7,9(11)-dien-3β-acetyloxy-24,25-diol (1), lanosta-7,9(11)-dien-3-oxo-24,26-diol-25-methoxy (2), and lanosta-8,20(22)-dien-3,11,23-trioxo-7β,15β-diol-26-oic acid methyl ester (3) by the analysis of 1D, 2D NMR, and HRESIMS spectroscopic data. All isolates were assayed for their cytotoxic activities using three human cancer cell lines (K562, BEL-7402, and SGC-7901) and seven lanostane triterpenoids (1, 2, 7, 13, 18, 22, and 24), and one ergostane steroid (34) showed definite cytotoxicity with IC₅₀ values that ranged from 6.64 to 47.63 μg/mL. Among these cytotoxic lanostane triterpenoids, compounds 2 and 13 showed general cytotoxicity against three human cancer cell lines, while compounds 1 and 18 exhibited significant selective cytotoxicity against K562 cells with IC₅₀ values of 8.59 and 8.82 μg/mL, respectively. Furthermore, the preliminary structure–cytotoxicity relationships was proposed. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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20 pages, 6915 KiB

Open AccessArticle

Transcriptome and Metabolome Analyses Provide Insights into the Flavonoid Accumulation in Peels of Citrus reticulata ‘Chachi’

by Jianmu Su, Tianhua Peng, Mei Bai, Haiyi Bai, Huisi Li, Huimin Pan, Hanjun He, Huan Liu and Hong Wu

Molecules 2022, 27(19), 6476; https://doi.org/10.3390/molecules27196476 - 01 Oct 2022

Cited by 4 | Viewed by 1848

Abstract

The quality of Chinese medicinal materials depends on the content of bioactive components, which are affected by the environmental factors of different planting regions. In this research, integrated analysis of the transcriptome and metabolome of C. reticulata ‘Chachi’ was performed in two regions, and three orchards were included in the analysis. In total, only 192 compounds were found in fresh peels, and among 18 differentially accumulated flavonoid metabolites, 15 flavonoids were enriched in peels from the Xinhui planting region. In total, 1228 genes were up-regulated in peels from Xinhui, including the CHS and GST genes, which are involved in the salt stress response. Overall, based on the correlation analysis of flavonoid content and gene expression in peels of C. reticulata ‘Chachi’, we concluded that the authenticity of the GCRP from Xinhui may be closely related to the higher content of naringin and narirutin, and the increase in the content of these may be due to the highly saline environment of the Xinhui region. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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Review

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17 pages, 1344 KiB

Open AccessReview

Challenges and Advances in the Bioproduction of L-Cysteine

by Daniel Alejandro Caballero Cerbon, Leon Gebhard, Ruveyda Dokuyucu, Theresa Ertl, Sophia Härtl, Ayesha Mazhar and Dirk Weuster-Botz

Molecules 2024, 29(2), 486; https://doi.org/10.3390/molecules29020486 - 18 Jan 2024

Viewed by 1295

Abstract

L-cysteine is a proteogenic amino acid with many applications in the pharmaceutical, food, animal feed, and cosmetic industries. Due to safety and environmental issues in extracting L-cysteine from animal hair and feathers, the fermentative production of L-cysteine offers an attractive alternative using renewable feedstocks. Strategies to improve microbial production hosts like Pantoea ananatis, Corynebacterium glutamicum, Pseudomonas sp., and Escherichia coli are summarized. Concerning the metabolic engineering strategies, the overexpression of feedback inhibition-insensitive L-serine O-acetyltransferase and weakening the degradation of L-cysteine through the removal of L-cysteine desulfhydrases are crucial adjustments. The overexpression of L-cysteine exporters is vital to overcome the toxicity caused by intracellular accumulating L-cysteine. In addition, we compiled the process engineering aspects for the bioproduction of L-cysteine. Utilizing the energy-efficient sulfur assimilation pathway via thiosulfate, fermenting cheap carbon sources, designing scalable, fed-batch processes with individual feedings of carbon and sulfur sources, and implementing efficient purification techniques are essential for the fermentative production of L-cysteine on an industrial scale. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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20 pages, 3985 KiB

Open AccessReview

Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium

by Xiaoling Zhang, Bingling Tang, Sijie Wen, Yitong Wang, Chengxue Pan, Lingbo Qu, Yulong Yin and Yongjun Wei

Molecules 2023, 28(20), 7173; https://doi.org/10.3390/molecules28207173 - 19 Oct 2023

Cited by 2 | Viewed by 1691

Abstract

Epimedium is a classical Chinese herbal medicine, which has been used extensively to treat various diseases, such as sexual dysfunction, osteoporosis, cancer, rheumatoid arthritis, and brain diseases. Flavonoids, such as icariin, baohuoside I, icaritin, and epimedin C, are the main active ingredients with diverse pharmacological activities. Currently, most Epimedium flavonoids are extracted from Epimedium plants, but this method cannot meet the increasing market demand. Biotransformation strategies promised huge potential for increasing the contents of high-value Epimedium flavonoids, which would promote the full use of the Epimedium herb. Complete biosynthesis of major Epimedium flavonoids by microbial cell factories would enable industrial-scale production of Epimedium flavonoids. This review summarizes the structures, pharmacological activities, and biosynthesis pathways in the Epimedium plant, as well as the extraction methods of major Epimedium flavonoids, and advancements in the biotransformation and complete microbial synthesis of Epimedium flavonoids, which would provide valuable insights for future studies on Epimedium herb usage and the production of Epimedium flavonoids. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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23 pages, 598 KiB

Open AccessReview

From Plant to Yeast—Advances in Biosynthesis of Artemisinin

by Le Zhao, Yunhao Zhu, Haoyu Jia, Yongguang Han, Xiaoke Zheng, Min Wang and Weisheng Feng

Molecules 2022, 27(20), 6888; https://doi.org/10.3390/molecules27206888 - 14 Oct 2022

Cited by 10 | Viewed by 4769

Abstract

Malaria is a life-threatening disease. Artemisinin-based combination therapy (ACT) is the preferred choice for malaria treatment recommended by the World Health Organization. At present, the main source of artemisinin is extracted from Artemisia annua; however, the artemisinin content in A. annua is only 0.1–1%, which cannot meet global demand. Meanwhile, the chemical synthesis of artemisinin has disadvantages such as complicated steps, high cost and low yield. Therefore, the application of the synthetic biology approach to produce artemisinin in vivo has magnificent prospects. In this review, the biosynthesis pathway of artemisinin was summarized. Then we discussed the advances in the heterologous biosynthesis of artemisinin using microorganisms (Escherichia coli and Saccharomyces cerevisiae) as chassis cells. With yeast as the cell factory, the production of artemisinin was transferred from plant to yeast. Through the optimization of the fermentation process, the yield of artemisinic acid reached 25 g/L, thereby producing the semi-synthesis of artemisinin. Moreover, we reviewed the genetic engineering in A. annua to improve the artemisinin content, which included overexpressing artemisinin biosynthesis pathway genes, blocking key genes in competitive pathways, and regulating the expression of transcription factors related to artemisinin biosynthesis. Finally, the research progress of artemisinin production in other plants (Nicotiana, Physcomitrella, etc.) was discussed. The current advances in artemisinin biosynthesis may help lay the foundation for the remarkable up-regulation of artemisinin production in A. annua through gene editing or molecular design breeding in the future. Full article

(This article belongs to the Special Issue Synthesis of Natural Products Using Engineered Plants and Microorganisms)

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