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Making small molecules in plants:A chassis for synthetic biology-based production of plant Natural products

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Journal of Integrative Plant Biology 2023年第2期65卷 417-443页

作者： Xinyu Liu Peijun Zhang Qiao Zhao Ancheng C.Huang Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes Department of BiologySchool of Life SciencesSUSTech-PKU Institute of Plant and Food ScienceSouthern University of Science and TechnologyShenzhen 518055China Shenzhen Institutes of Advanced Technology(SIAT) the Chinese Academy of SciencesShenzhen 518055China

Plant Natural products have been extensively exploited in food,medicine,flavor,cosmetic,renewable fuel,and other industrial sectors.Synthetic biology has recently emerged as a promising means for the cost-effective and sustainable production of Natural products.Compared with engineering microbes for the production of plant Natural products,the potential of plants as chassis for producing these compounds is underestimated,largely due to challenges encountered in engineering plants.Knowledge in plant engineering is instrumental for enabling the effective and efficient production of valuable phytochemicals in plants,and also paves the way for a more sustainable future agriculture.In this manuscript,we briefly recap the biosynthesis of plant Natural products,focusing primarily on industrially important terpenoids,alkaloids,and phenylpropanoids.We further summarize the plant hosts and strategies that have been used to engineer the production of Natural products.The challenges and opportunities of using plant synthetic biology to achieve rapid and scalable production of high-value plant Natural products are also discussed.

关键词： biosynthesis Natural products plant engineering synthetic biology

Natural products:potential therapeutic agents for atherosclerosis

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Chinese Journal of natural Medicines 2022年第11期20卷 830-845页

作者： CHENG Xiaobei ZHAO Caili JIN Zhiwei HU Jianping ZHANG Zhenzhen ZHANG Chao State Key Laboratory of natural Medicines and Jiangsu Key Laboratory of Bioactive natural Product Research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China Institute of Veterinary Medicine Jiangsu Academy of Agricultural SciencesNanjing 210014China

Atherosclerosis(AS)is an invisible killer among cardiovascular diseases(CVD),which has seriously threatened the life of quality.The complex pathogenesis of AS involves multiple interrelated events and cell types,such as macrophages,endothelial cells,vascular smooth muscle cells and immune cells.Currently,the efficacy of recommended statin treatment is not satisfactory.Natural products(NPs)have attracted increasing attention with regard to their broad structural diversity and biodiversity,which makes them a promising library in the demand for lead compounds with cardiovascular protective bio-activity.NPs can preclude the development of AS by regulating lipid metabolism,ameliorating inflammation,stabilizing plaques,and remodeling the gut microbiota,which lays a foundation for the application of NPs in clinical therapeutics.

关键词： Atherosclerosis Cardiovascular diseases Pathogenesis Target Natural products

Emerging role of Natural products in cancer immunotherapy

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1163-1185页

作者： Songtao Dong Xiangnan Guo Fei Han Zhonggui He Yongjun Wang Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Cancer immunotherapy has become a new generation of anti-tumor treatment,but its indications still focus on several types of tumors that are sensitive to the immune system.Therefore,effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy.Natural products are reported to have this effect on cancer immunotherapy,including cancer vaccines,immune-check points inhibitors,and adoptive immune-cells therapy.And the mechanism of that is mainly attributed to the remodeling of the tumorimmunosuppressive microenvironment,which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy.Therefore,this review summarizes and concludes the Natural products that reportedly improve cancer immunotherapy and investigates the mechanism.And we found that saponins,polysaccharides,and flavonoids are mainly three categories of Natural products,which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment.Besides,this review also collected the studies about nano-technology used to improve the disadvantages of Natural products.All of these studies showed the great potential of Natural products in cancer immunotherapy.

关键词： Natural products Cancer immunotherapy Immunosuppressive microenvironment Cancer vaccines Immuno-check points Adoptive immune-cells transfer immunotherapy

Anti-tumor pharmacology of Natural products targeting mitosis

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Cancer Biology & Medicine 2022年第6期19卷 774-801页

作者： Manru Huang Caiyan Liu Yingying Shao Shiyue Zhou Gaoyong Hu Shuangshuang Yin Weiling Pu Haiyang Yu Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae Ministry of EducationTianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Cancer has been an insurmountable problem in the history of medical science.The uncontrollable proliferation of cancer cells is one of cancers main characteristics,which is closely associated with abn ormal mitosis.Targeting mitosis is an effective method for cancer treatment.This review summarizes several Natural products with anti-tumor effects related to mitosis,focusing on targeting microtubulin,inducing DNA damage,and modulating mitosis-associated kinases.Furthermore,the main disadvantages of several typical compounds,including drug resistance,toxicity to non-tumor tissues,and poor aqueous solubility and pharmacokinetic properties,are also discussed,together with strategies to address them.Improved understanding of cancer cell mitosis and Natural products may pave the way to drug development for the treatment of cancer.

关键词： Tumor mitosis Natural products mechanism pharmacology

New opportunities and challenges of Natural products research:When target identification meets single-cell multiomics

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4011-4039页

作者： Yuyu Zhu Zijun Ouyang Haojie Du Meijing Wang Jiaojiao Wang Haiyan Sun Lingdong Kong Qiang Xu Hongyue Ma Yang Sun College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Institute of Marine Biomedicine School of Food and DrugShenzhen PolytechnicShenzhen 518055China State Key Laboratory of Pharmaceutical Biotechnology School of Life ScienceNanjing UniversityNanjing 210023China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou 221004China

Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of Natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of Natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of Natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of Natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

关键词： Natural products Traditional Chinese medicine Molecular mechanism Inflammatorydiseases Cancer Targetidentification Single-cell multiomics Biosynthesis

Multiscale engineering of microbial cell factories: A step forward towards sustainable Natural products industry

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Synthetic and Systems Biotechnology 2022年第1期7卷 586-601页

作者： Muhammad Hammad Hussain Muhammad Zubair Mohsin Waqas Qamar Zaman Junxiong Yu Xueli Zhao Yanlong Wei Yingping Zhuang Ali Mohsin Meijin Guo State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai200237PR China Institute of Environmental Sciences and Engineering School of Civil and Environmental EngineeringNational University of Sciences and Technology(NUST)Sector H-12Islamabad44000Pakistan

Microbial cell factories(bacteria and fungi)are the leading producers of beneficial Natural products such as lycopene,carotene,herbal medicine,and biodiesel etc.These microorganisms are considered efficient due to their effective bioprocessing strategy(monoculture-and consortial-based approach)under distinct processing conditions.Meanwhile,the advancement in genetic and process optimization techniques leads to enhanced biosynthesis of Natural products that are known functional ingredients with numerous applications in the food,cosmetic and medical industries.natural consortia and monoculture thrive in nature in a small proportion,such as wastewater,food products,and soils.In similitude to natural consortia,it is possible to engineer artificial microbial consortia and program their behaviours via synthetic biology tools.Therefore,this review summarizes the optimization of genetic and physicochemical parameters of the microbial system for improved production of Natural products.Also,this review presents a brief history of natural consortium and describes the functional properties of monocultures.This review focuses on synthetic biology tools that enable new approaches to design synthetic consortia;and highlights the syntropic interactions that determine the performance and stability of synthetic consortia.In particular,the effect of processing conditions and advanced genetic techniques to improve the productibility of both monoculture and consortial based systems have been greatly emphasized.In this context,possible strategies are also discussed to give an insight into microbial engineering for improved pro-duction of Natural products in the future.In summary,it is concluded that the coupling of genomic modifications with optimum physicochemical factors would be promising for producing a robust microbial cell factory that shall contribute to the increased production of Natural products.

关键词： Genetic and process optimization techniques Monoculture Natural products Synthetic consortia Synthetic biology tools

Natural products in cosmetics

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Natural products and Bioprospecting 2022年第1期12卷 635-677页

作者： Ji-Kai Liu Wuhan Institute of Health Shenzhen Moore Vaporization Health&Medical Technology Co.Ltd.Wuhan 430074People’s Republic of China School of Pharmaceutical Sciences South-Central University for NationalitiesWuhan 430074People’s Republic of China

The global cosmetics market reached US$500 billion in 2017 and is expected to exceed US$800 billion by 2023,at around a 7%annual growth rate.The cosmetics industry is emerging as one of the fastest-growing industries of the past decade.Data shows that the Chinese cosmetics market was US$60 billion in 2021.It is expected to be the world’s number one consumer cosmetics market by 2050,with a size of approximately US$450 billion.The influence of social media and the internet has raised awareness of the risks associated with the usage of many chemicals in cosmetics and the health benefits of Natural products derived from plants and other natural resources.As a result,the cosmetic industry is now paying more attention to Natural products.The present review focus on the possible applications of Natural products from various biological sources in skin care cosmetics,including topical care products,fragrances,moisturizers,UV protective,and anti-wrinkle products.In addition,the mechanisms of targets for evaluation of active ingredients in cosmetics and the possible benefits of these bioactive compounds in rejuvenation and health,and their potential role in cosmetics are also discussed.

关键词： Natural products Cosmetics Skin whitening agents Skin anti-aging agents Moisturizers

Chiral Pool Guided Syntheses of Polycyclic Natural products

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Chinese Journal of Chemistry 2022年第3期40卷 407-418页

作者： Shaomin Fu Bo Liu Key Laboratory of Green Chemistry&Technology of Ministry of Education College of ChemistrySichuan University29 Wongjiang Rd.ChengduSichuan 610064China

Chiral pools have been commonly utilized as inexpensive and versatile building blocks in organic synthesis.In this account,we provide an overview of our recent synthetic efforts toward polycyclic Natural products using chiral natural small molecules(chiral pool)as starting materials.Key achievements during our syntheses include intermolecular Diels-Alder/intramolecular hetero-Diels-Alder cascade to enable modification of previously proposed biosynthetic pathway of bolivianine,Diels-Alder-type dimerization through a conjugated furanyl diene intermediate to achieve three types of lindenane[4+2]dimers,Iron-catalyzed reductive aldol reaction to construct core of rumphellclovane E and[3,3]-rearrangement along with vinylo-gous Pummerer rearrangement to make epoxyquinol substructure of JBIR-23/-24.In the final,the outlook is also presented.

关键词： Chiral pool Natural products Total synthesis Polycylic Cascade reaction

Hypoglycemic Natural products with in vivo activities and their mechanisms:a review

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Food Science and Human Wellness 2022年第5期11卷 1087-1100页

作者： Wenyi Ma Longgao Xiao Haiyang Liu Xiaojiang Hao State Key Laboratory of Phytochemistry and Plant Resources in West China Yunnan Key Laboratory of Natural Medicinal ChemistryKunming Institute of BotanyChinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Diabetes mellitus(DM) is a metabolic disorder disease,and the number of diabetic patients will reach 578 million by 2030 predictably.Currently,8 classes of small molecular drugs are used for treating diabetes.However,these drugs cannot completely meet patients ’ needs,due to diabetic complications need to be addressed along with diabetes,such as nephropathy,and cardiovascular diseases.Besides,more types of drugs need to be provided for more choices.Hence,scientists still seek lead compounds with hypoglycemic effects.Natural products(NPs) are a reservoir of diverse structures and bioactivities with low toxicity and less side effects.And some of them show effects on diabetic complications,which is a significant idea for drug development.This review aims to summarize Natural products with hypoglycemic effects and their details,such as potential mechanisms,biological data,and particularly their advantages in treating diabetes.Considering the huge number of NPs was reported with anti-diabetic activity,and some of them need to be re-validated,this review focuses on the bioactive compounds with in vivo activities.In the end,the trend of Natural products treating diabetes was discussed.We hope this review provide a comprehensive and convincing summary,thus lending support to anti-diabetic Natural products research.

关键词： Diabetes Natural products Hypoglycemic effects Mechanism