Review
Biology
Vonny Salim, Sara-Alexis Jarecki, Marshall Vick, Ryan Miller
Summary: Monoterpene indole alkaloids (MIAs) are a diverse family of over 3000 plant natural products with a wide range of medical applications. However, their low abundance in natural sources and complex synthesis processes hinder further utilization. Metabolic engineering of MIAs biosynthesis in heterologous hosts is an attractive approach to increase yield and expand chemical diversity. This review discusses recent advances, strategies, current issues, and future developments in manufacturing MIAs through synthetic biology approaches.
Review
Biotechnology & Applied Microbiology
Amir Y. Alwali, Elizabeth Parkinson
Summary: Actinobacteria are a significant group of bacteria that produce important bioactive compounds. Environmental factors and small molecule elicitors can induce the production of secondary metabolites from actinobacteria, especially those that are typically undetectable.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Dongdong Zhao, Xinna Zhu, Hang Zhou, Naxin Sun, Ting Wang, Changhao Bi, Xueli Zhang
Summary: Effective metabolic pathways are crucial for efficient cell factories, and utilizing CRISPR technology in pathway engineering can enhance efficiency, reduce costs, and simplify target customization. This technology has been proven to be robust and effective in various organisms.
METABOLIC ENGINEERING
(2021)
Review
Integrative & Complementary Medicine
Yang Li-Yang, Gong Qiang, Guo Jian-Quan, Li Gui-Lan
Summary: Mushrooms are rich in bioactive natural compounds, and using microbes as production hosts for these compounds offers an alternative and sustainable approach. This review focuses on the biosynthetic pathways of mushroom-derived natural compounds and the use of microbes as production hosts for these compounds.
CHINESE JOURNAL OF NATURAL MEDICINES
(2021)
Review
Biochemistry & Molecular Biology
Younghoon Kim, Sandip Sengupta, Taebo Sim
Summary: The review discusses the anti-tumor activities and synthetic routes of natural and synthetic lactones, highlighting their potential as anticancer agents and aiming to advance the process of oncology drug discovery based on natural products.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Sean F. Sullivan, Anuj Shetty, Tharun Bharadwaj, Naveen Krishna, Vikas D. Trivedi, Venkatesh Endalur Gopinarayanan, Todd C. Chappell, Daniel M. Sellers, R. Pravin Kumar, Nikhil U. Nair
Summary: Engineering the utilization of non-native substrates in industrial microbes provides a way to use renewable sources for bioprocesses. Previous research has shown that activating the GAL regulon in Saccharomyces cerevisiae during growth on the non-native substrate xylose enhances gene expression and growth compared to constitutive overexpression of the same pathway. However, this method was not easily adaptable to other non-native substrates. In this study, a variant of Gal3p called Gal3pMC was constructed, which can activate the GAL regulon with diverse substrates and mimic the dynamics of the native system. Testing this regulon approach with non-native lignocellulosic sugars resulted in higher growth rates and final cell densities compared to constitutive overexpression. The co-utilization of multiple non-native substrates suggests that this regulon approach could be universally beneficial for engineering synthetic heterotrophy.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Irene Otero-Muras, Pablo Carbonell
Summary: Metabolic engineering involves optimizing processes from single-cell to fermentation to increase production of valuable chemicals. A systems approach has accelerated scaling from rapid prototyping to industrial production, with automated DNA assembly reducing time from conception to production. The success of metabolic engineering often relies on retrobiosynthetic protocols and dynamic regulation strategies assembled as genetic circuits in host strains.
METABOLIC ENGINEERING
(2021)
Review
Biotechnology & Applied Microbiology
Kim-Ngan T. Tran, Ashokkumar Kumaravel, Soon Ho Hong
Summary: Metabolic engineering has become an attractive choice for efficient bio-refinery processes or biochemical production. However, engineered metabolic pathways often suffer from flux imbalances due to a lack of corresponding regulatory mechanisms. Protein scaffolds have been created to co-localize proteins and enhance metabolic productivity.
BIOTECHNOLOGY AND BIOPROCESS ENGINEERING
(2023)
Review
Plant Sciences
Lachlan Dow, Marta Gallart, Margaret Ramarajan, Simon R. Law, Louise F. Thatcher
Summary: In the search for new crop protection microbial biocontrol agents, isolates from the genus Streptomyces are commonly found. Streptomyces are natural soil dwellers and have evolved as plant symbionts producing specialized metabolites with antibiotic and antifungal activities. The investigation of factors stimulating the production and release of Streptomyces bioactive compounds is commonly conducted in vitro, but recent research is starting to shed light on their behavior in planta, under different conditions. This review focuses on the methods by which Streptomyces biocontrol agents employ specialized metabolites as a defense against plant pathogens, the signals shared in the tripartite system, and new approaches for identification and understanding of these metabolites.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Gahyeon Ryu, Gi Bae Kim, Taeho Yu, Sang Yup Lee
Summary: The establishment of a bio-based circular economy is crucial for addressing the climate crisis and promoting sustainable development. Designing metabolic pathways for microbial cell factories is essential, and computer-supported tools and deep learning techniques can aid in pathway prediction and enzyme discovery. Leveraging these computational tools and strategies, particularly the capabilities of deep learning, has the potential to accelerate the advent of a bio-based circular economy.
METABOLIC ENGINEERING
(2023)
Review
Biochemistry & Molecular Biology
Dongsoo Yang, Hyunmin Eun, Cindy Pricilia Surya Prabowo
Summary: Polyketides, a type of natural products, have versatile applications such as pharmaceuticals, nutraceuticals, and cosmetics. Aromatic polyketides, including type II and III polyketides, are important chemicals for human health, such as antibiotics and anticancer agents. However, they are mainly produced from challenging sources like soil bacteria or plants. To address this issue, metabolic engineering and synthetic biology have been used to efficiently engineer model microorganisms for enhanced production of aromatic polyketides. This review discusses the recent advancements and future prospects of metabolic engineering and synthetic biology strategies in the production of type II and type III polyketides in model microorganisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Qing-Bin Wu, Xiao-Ying Zhang, Xin-Ai Chen, Yong-Quan Li
Summary: By deleting competitive pathways, refactoring the FK506 biosynthetic gene cluster, and adding nutrients, a strategy for hyper-production of FK506 was successfully developed, leading to the construction of a hyper-production strain L19-9. This strategy can be generally applicable to other Streptomyces for improving FK506 production and streamlining hyper-production of other valuable secondary metabolites.
MICROBIAL CELL FACTORIES
(2021)
Article
Computer Science, Software Engineering
Jevgenija Pantiuchina, Bin Lin, Fiorella Zampetti, Massimiliano Di Penta, Michele Lanza, Gabriele Bavota
Summary: The researchers manually coded rejection reasons from 330 refactoring-related pull requests, resulting in a comprehensive taxonomy consisting of 26 refactoring-related rejection reasons and 21 process-related rejection reasons. The taxonomy provides valuable insights for developers and highlights several directions for improving refactoring recommenders.
ACM TRANSACTIONS ON SOFTWARE ENGINEERING AND METHODOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Khorshed Alam, Jinfang Hao, Youming Zhang, Aiying Li
Summary: There is an immediate need for innovative approaches, strategies, and techniques to discover new microbial-derived natural products (NPs) with novel or enhanced biological properties due to the low productivity and high cost of traditional drug discovery pipelines from natural bioresources. DNA sequencing technology and bioinformatics tools are revealing untapped microbial cryptic biosynthetic gene clusters, enabling genome mining for NP discovery from microorganisms. New approaches and strategies in synthetic biology offer great potentials for the generation of new NPs with improved and desired functions through engineering synthetic systems.
BIOTECHNOLOGY ADVANCES
(2021)
Review
Biotechnology & Applied Microbiology
Wen-Hai Xie, Hong-Kuan Deng, Jie Hou, Li-Juan Wang
Summary: Key points center dot Synthetic sRNAs can be rationally designed based on modular structures of natural sRNAs. center dot Synthetic sRNAs were widely used for metabolic engineering in various microorganisms. center dot Several technological improvements made the synthetic sRNA strategy more applicable.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Mindong Liang, Zilong Li, Weishan Wang, Jiakun Liu, Leshi Liu, Guoliang Zhu, Loganathan Karthik, Man Wang, Ke-Feng Wang, Zhong Wang, Jing Yu, Yuting Shuai, Jiaming Yu, Lu Zhang, Zhiheng Yang, Chuan Li, Qian Zhang, Tong Shi, Liming Zhou, Feng Xie, Huanqin Dai, Xueting Liu, Jingyu Zhang, Guang Liu, Ying Zhuo, Buchang Zhang, Chenli Liu, Shanshan Li, Xuekui Xia, Yaojun Tong, Yanwen Liu, Gil Alterovitz, Gao-Yi Tan, Li-Xin Zhang
NATURE COMMUNICATIONS
(2019)
Correction
Biotechnology & Applied Microbiology
Weishan Wang, Shanshan Li, Zilong Li, Jingyu Zhang, Keqiang Fan, Gaoyi Tan, Guomin Ai, Sin Man Lam, Guanghou Shui, Zhiheng Yang, Hongzhong Lu, Pinjiao Jin, Yihong Li, Xiangyin Chen, Xuekui Xia, Xueting Liu, H. Kathleen Dannelly, Chen Yang, Yi Yang, Siliang Zhang, Gil Alterovitz, Wensheng Xiang, Lixin Zhang
NATURE BIOTECHNOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Weishan Wang, Shanshan Li, Zilong Li, Jingyu Zhang, Keqiang Fan, Gaoyi Tan, Guomin Ai, Sin Man Lam, Guanghou Shui, Zhiheng Yang, Hongzhong Lu, Pinjiao Jin, Yihong Li, Xiangyin Chen, Xuekui Xia, Xueting Liu, H. Kathleen Dannelly, Chen Yang, Yi Yang, Siliang Zhang, Gil Alterovitz, Wensheng Xiang, Lixin Zhang
NATURE BIOTECHNOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Zhiheng Yang, Qingqing Sun, Gaoyi Tan, Quanwei Zhang, Zhengduo Wang, Chuan Li, Fengxian Qi, Weishan Wang, Lixin Zhang, Zilong Li
Summary: The researchers successfully produced riboflavin in the thermophile Geobacillus thermoglucosidasius at elevated temperatures through metabolic engineering, demonstrating the potential for high-temperature cell factories for riboflavin production in this promising host.
MICROBIAL BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Xiangxiang Zhao, Shanshan Li, Guang Liu, Zhong Wang, Zhiheng Yang, Quanwei Zhang, Mindong Liang, Jiakun Liu, Zilong Li, Yaojun Tong, Guoliang Zhu, Xinye Wang, Lan Jiang, Weishan Wang, Gao-Yi Tan, Lixin Zhang
Summary: This study introduces a versatile biosensing platform that combines CRISPR-Cas with aptamers for detecting proteins and small molecules in human serum. The platform offers advantages of simplicity, sensitivity, short detection time, and low cost, showing great potential in diverse analyte detection.
Article
Biotechnology & Applied Microbiology
Lan Jiang, Guoliang Zhu, Jianying Han, Chengjian Hou, Xue Zhang, Zhixin Wang, Weize Yuan, Kangjie Lv, Zhanren Cong, Xinye Wang, Xiangyin Chen, Loganathan Karthik, Huanting Yang, Xuyuan Wang, Gaoyi Tan, Guang Liu, Liya Zhao, Xuekui Xia, Xiangyang Liu, Shushan Gao, Lei Ma, Mei Liu, Biao Ren, Huanqin Dai, Ronald J. Quinn, Tom Hsiang, Jingyu Zhang, Lixin Zhang, Xueting Liu
Summary: The study identified a unique BFTS sub-clade critical to the formation of a 5-15 trans-fused bicyclic sesterterpene and revealed that phytopathogenic fungi can serve as important sources of active terpenoids through systematic analysis of BFTS biosynthetic gene clusters.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Biochemical Research Methods
Shanshan Li, Bowen Yang, Gao-Yi Tan, Li-Ming Ouyang, Shiwen Qiu, Weishan Wang, Wensheng Xiang, Lixin Zhang
Summary: Natural product derived polyketide pesticides have gained popularity worldwide due to their high efficacy, eco-friendly nature, and safety profile, with advancements in the development of such pesticides from actinomycetes in recent decades. These pesticides, such as avermectins, spinosyns, polynactins, tetramycin, and their analogues, have shown successful applications in crop protection, with continuous improvement driven by biotechnological advances.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Shaohua Li, Jianke Huang, Liang Ji, Cheng Chen, Ping Wu, Wei Zhang, Gaoyi Tan, Haizhen Wu, Jianhua Fan
Summary: The study optimized the cultivation process for red alga Porphyridium purpureum using a light distribution model, showing that the Hyperbolic law is more flexible in handling light distribution. Furthermore, it was found that the content of intracellular phycobiliprotein has a significant impact on light distribution, and higher biomass concentrations reduce this impact.
ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
(2021)
Article
Biotechnology & Applied Microbiology
Tong Shi, Lu Zhang, Mindong Liang, Weishan Wang, Kefeng Wang, Yue Jiang, Jing Liu, Xinwei He, Zhiheng Yang, Haihong Chen, Chuan Li, Dongyuan Lv, Liming Zhou, Biqin Chen, Dan Li, Li-Xin Zhang, Gao-Yi Tan
Summary: In this study, several native promoters from Rhodobacter sphaeroides JDW-710 were characterized, with two showing significantly higher activity than the commonly used tac promoter. A synthetic promoter library was also created, leading to successful modulation of the Q10 synthetic pathway in JDW-710 and increased production yields.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Xiangxiang Zhao, Zhengduo Wang, Bowen Yang, Zilong Li, Yaojun Tong, Yuhai Bi, Zhenghong Li, Xuekui Xia, Xiangyin Chen, Lixin Zhang, Weishan Wang, Gao-Yi Tan
Summary: The study introduces a new antigen detection method that combines CRISPR/Cas12a and aptamers, providing ultra-sensitive, fast, and stable detection capabilities. The method was able to detect the SARS-CoV-2 antigen nucleocapsid protein at the single virus level in saliva or serum samples within 20 minutes, showing promise for general applications in CRISPR/Cas12a-aptamer-based detection.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mindong Liang, Leshi Liu, Fei Xu, Xiaoqian Zeng, Runjun Wang, Jinling Yang, Weishan Wang, Loganathan Karthik, Jiakun Liu, Zhiheng Yang, Guoliang Zhu, Shuliu Wang, Linquan Bai, Yaojun Tong, Xueting Liu, Min Wu, Li-Xin Zhang, Gao-Yi Tan
Summary: In this study, a method named CAT-FISHING was developed to directly capture large biosynthetic gene clusters (BGCs) by combining Cas12a and the advanced features of bacterial artificial chromosome library construction. Several large BGCs from different actinomycetal genomic DNA samples were efficiently captured using CAT-FISHING, and a new macrolactam compound with promising anticancer activity was discovered.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Yuting Shuai, Yi Ju, Yuanhang Li, Dini Ma, Lan Jiang, Jingyu Zhang, Gao-Yi Tan, Xueting Liu, Shenlin Wang, Lixin Zhang, Guang Liu
Summary: SENSOR is a rapid nucleic acid detection method that utilizes phosphorothioate (PT)-DNA and sulfur binding domain (SBD) to specifically bind double-stranded PT-modified DNA. By using PT-DNA oligo and SBD as targeting module, SENSOR generates luminescence signal within 10 minutes by linking with split luciferase reporter. The technique achieved attomolar sensitivity combined with amplification procedure and can discriminate single nucleotide polymorphisms (SNP).
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Zhiheng Yang, Zilong Li, Bixiao Li, Ruihong Bu, Gao-Yi Tan, Zhengduo Wang, Hao Yan, Zhenguo Xin, Guojian Zhang, Ming Li, Hua Xiang, Lixin Zhang, Weishan Wang
Summary: This study identified a thermophilic type I-B CRISPR-Cas system that can efficiently perform transcriptional repression and DNA cleavage, and the activity can be switched by adjusting the length of crRNA. The researchers developed an orthogonal tool for genome editing and transcriptional repression using this system in both thermophile and mesophile hosts. By implementing temporal multiplexed repression, they achieved high efficiency in generating supercompetent P. thermoglucosidasius cells and successfully constructed a thermophilic riboflavin cell factory with the highest titers in high temperature fermentation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Xiaoqian Zeng, Shuliu Wang, Mindong Liang, Weishan Wang, Yue Jiang, Fei Xu, Leshi Liu, Hao Yan, Yaojun Tong, Lixin Zhang, Gao-Yi Tan
Summary: This study presents an in vitro CRISPR-Cas12a-mediated protocol for direct cloning of large DNA fragments, which is important for discovering natural product-based drugs in high GC content microorganisms, such as Actinobacteria. The detailed steps include crRNA design and preparation, genomic DNA isolation, construction and linearization of CRISPR-Cas12a cleavage and capture plasmid, as well as ligation and transformation of target biosynthetic gene cluster (BGC) and plasmid DNA, and screening for positive clones. For complete details on the use and execution of this protocol, please refer to the study by Liang et al.
Article
Biotechnology & Applied Microbiology
Lu Zhang, Leshi Liu, Ke-Feng Wang, Lan Xu, Liming Zhou, Weishan Wang, Chuan Li, Zheng Xu, Tong Shi, Haihong Chen, Yuanhang Li, Hui Xu, XiuLiang Yang, Zhichun Zhu, Biqin Chen, Dan Li, Guanghuang Zhan, Si-Liang Zhang, Li-Xin Zhang, Gao-Yi Tan
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2019)
