Review
Biochemistry & Molecular Biology
Hanghang Lou, Lifei Hu, Hongyun Lu, Tianyu Wei, Qihe Chen
Summary: Flavonoids, plant secondary metabolites with polyphenol structure, exhibit diverse biological activities and find wide applications, but traditional sources are inadequate. Recent advancements in synthetic metabolic engineering with microorganisms as hosts have enabled the production of flavonoids to meet current demands.
Review
Agricultural Engineering
Shenghu Zhou, Nana Ding, Runhua Han, Yu Deng
Summary: This article discusses the strategies to maximize the biosynthesis of organic acids through metabolic engineering and fermentation optimization. These strategies mainly focus on the synthetic pathway engineering based on the TCA and glyoxylate pathways, as well as techniques like organic acid secretion enhancement and renewable substrate-based fermentation. Further strategies to construct high-productivity and acid-resistant strains are also discussed.
BIORESOURCE TECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Yanyan Wang, Linxia Liu, Zhaoxia Jin, Dawei Zhang
Summary: Vitamins are essential for maintaining normal metabolism and health, with wide applications in various industries. Using microbial cell factories for vitamin production is both environmentally friendly and economically sustainable, covering water-soluble and fat-soluble vitamins.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Young Jin Ko, Myeong-Eun Lee, Byeong-Hyeon Cho, Minhye Kim, Jeong Eun Hyeon, Joo Hee Han, Sung Ok Han
Summary: Porphyrins, phycobilins, and their proteins have potential applications in various fields, but their high price and petroleum-based synthesis limit their commercial use. Recent studies have focused on using microbial cell factories to produce these compounds from renewable carbon sources. This review summarizes the advances in bioproduction of porphyrins, phycobilins, and their proteins, discusses metabolic regulations, and addresses future challenges and perspectives. It aims to provide solutions and insights for their industrial application in future research.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Green & Sustainable Science & Technology
Zihe Liu, Hamideh Moradi, Shuobo Shi, Farshad Darvishi
Summary: Sustainable production of biofuels has become an attractive alternative to fossil fuels, with increasing interest in metabolic engineering of yeasts for biofuel production. Recent advancements in metabolic engineering have enabled the commercial production of new energy-dense biofuels using yeasts and synthetic biology tools.
RENEWABLE & SUSTAINABLE ENERGY REVIEWS
(2021)
Review
Biotechnology & Applied Microbiology
Shumin Xu, Song Gao, Yingfeng An
Summary: Pigments, such as carotenoids and melanins, are used in various aspects of daily life. The use of synthetic biology and metabolic engineering to construct microbial cell factories has advantages, such as a well-defined genetic background and rapid cell culture. However, the technical means for engineering microbial cell factories for pigment production and metabolic regulation processes have not been systematically analyzed. This review summarizes recent studies on the construction, modification, and regulation of synthetic pathways for microbial synthesis of pigments, providing new ideas for improving microbial production of natural pigments in the future.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Chemistry, Multidisciplinary
Zeinu Mussa Belew, Michal Poborsky, Hussam Hassan Nour-Eldin, Barbara Ann Halkier
Summary: Transport engineering strategies alter the expression of transporter proteins to change the distribution of metabolites within an organism. The production of plant specialized metabolites in microbial cell factories faces challenges such as premature pathway termination, feedback inhibition, low yields, and poor connectivity between subcellular compartments. This article highlights recent examples of transport engineering in microbial cell factories and proposes future research directions to advance the field.
CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Pei Zhou, Cong Gao, Wei Song, Wanqing Wei, Jing Wu, Liming Liu, Xiulai Chen
Summary: The engineering status of protein is crucial for the efficient bioproduction in microbial cell factories. Strategies such as protein engineering, protein modification, and protein assembly can effectively modify the protein status and enhance production efficiency.
BIOTECHNOLOGY ADVANCES
(2024)
Review
Biotechnology & Applied Microbiology
Eric Fordjour, Emmanuel Osei Mensah, Yunpeng Hao, Yankun Yang, Xiuxia Liu, Ye Li, Chun-Li Liu, Zhonghu Bai
Summary: This review focuses on novel strategies for improving microbial cell factory performance, including improving transcriptional and translational efficiencies, enzyme engineering, high-throughput screening, chromosomal integration, metabolite tolerance, and pathway modularization.
BIORESOURCES AND BIOPROCESSING
(2022)
Review
Biotechnology & Applied Microbiology
Qiang Ding, Chao Ye
Summary: Advanced techniques in synthetic biology and metabolic engineering have highlighted the potential of using filamentous bacteria, yeasts, and fungi as promising chassis cells for chemical production. However, their industrial application still faces significant challenges.
MICROBIAL CELL FACTORIES
(2023)
Article
Food Science & Technology
Daniela Gomes, Ligia R. Rodrigues, Joana L. Rodrigues
Summary: Prenylflavonoids are bioactive compounds with limited natural sources. Using microorganisms as cell factories is a faster and cheaper alternative for their production. Saccharomyces cerevisiae and Escherichia coli can be used as suitable chassis, but challenges remain in terms of yield and titer.
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Natalja Kulagina, Nicolas Papon, Vincent Courdavault
Summary: Plants have long been a valuable source of natural products, but low accumulation of compounds in plants has been a challenge for production costs and supply. Recent advancements in metabolic engineering of microorganisms offer hope for the efficient production of these molecules at an industrial scale.
Review
Biotechnology & Applied Microbiology
Lukas A. Rettenbacher, Klaudia Arauzo-Aguilera, Luisa Buscajoni, Angel Castillo-Corujo, Borja Ferrero-Bordera, Aliki Kostopoulou, Rafael Moran-Torres, David Nunez-Nepomuceno, Ayseguel OEktem, Arianna Palma, Beatrice Pisent, Martina Puricelli, Tobias Schilling, Aatir A. Tungekar, Jonathan Walgraeve, David Humphreys, Tobias von der Haar, Brigitte Gasser, Diethard Mattanovich, Lloyd Ruddock, Jan Maarten van Dijl
Summary: The biopharmaceutical market is experiencing rapid growth, with mammalian cells and microorganisms competing for market dominance. While mammalian cells have been favored in antibody-based therapies, extensive research has increased our understanding of microbes and emerging therapeutic molecules are making them more viable. This review compares four microbial production hosts and explores their secretion and post-translational modification capabilities, as well as discussing the impact of tools like omics and systems biology, alternative production systems, and emerging biotherapeutics.
TRENDS IN BIOTECHNOLOGY
(2022)
Review
Agricultural Engineering
Aravind Madhavan, K. B. Arun, Raveendran Sindhu, Bipin G. Nair, Ashok Pandey, Mukesh Kumar Awasthi, George Szakacs, Parameswaran Binod
Summary: The increasing demand for renewable biofuel substitutes and the need for innovative energy fuels that have characteristics similar to fossil-derived fuels have led to extensive research on metabolic and genetic engineering technologies. Efficient microbes for bioenergy synthesis require the ability to consume large amounts of carbon substrate, transfer various carbohydrates through efficient metabolic pathways, withstand inhibitory components and other degradation compounds, and improve metabolic fluxes. This review provides a comprehensive perspective on the trends and advances in metabolic and genetic engineering technologies for advanced biofuel synthesis.
BIORESOURCE TECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Zhengshan Luo, Yifan Yan, Shanshan Du, Yifan Zhu, Fei Pan, Rui Wang, Zheng Xu, Xiaoqi Xu, Sha Li, Hong Xu
Summary: Bacillus amyloliquefaciens, a Gram-positive bacterium, has unique characteristics that make it suitable for industrial applications. Through systems biology and synthetic biology techniques, its productivity characteristics have been optimized. Researchers discuss the potential advantages and recent advancements of B. amyloliquefaciens as a platform for metabolic engineering and industrial applications.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Sudha Shukal, Xiao Hui Lim, Congqiang Zhang, Xixian Chen
Summary: This study optimized the design of homology arms for gene deletion in E. coli BL21 and successfully applied it to edit the genome for increasing lycopene production.
MICROBIAL CELL FACTORIES
(2022)
Review
Biotechnology & Applied Microbiology
Ari Dwijayanti, Congqiang Zhang, Chueh Loo Poh, Thomas Lautier
Summary: Light-sensitive proteins play a crucial role in controlling cellular behaviors. Exploration and engineering of these proteins have contributed to the expansion of optogenetic toolboxes, enabling dynamic regulation of cells. Recent advancements include the design of complex systems incorporating multiple photoreceptors to coordinate cellular responses.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Congqiang Zhang, Christoph Ottenheim, Melanie Weingarten, LiangHui Ji
Summary: The global shift towards sustainability has led to the exploration of alternative feedstocks for biomanufacturing. C1 and C2 substrates, such as CO2, CO, methane, formate, methanol, acetate, and ethanol, are gaining attention due to their natural abundance and low production cost. Advances in metabolic engineering and synthetic biology have improved the efficiency of using these feedstocks by microbes, which can be further engineered to convert them into valuable products.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Choon Boon Cheong, GuangRong Peh, Yifeng Wei, T. Rehka, Ee Lui Ang, Huimin Zhao, Congqiang Zhang, Yee Hwee Lim
Summary: In this study, candidate sesquiterpene synthases were identified from the genome of the saffron milk cap mushroom L. deliciosus and expressed in a sesquiterpene-overproducing E. coli strain. The researchers discovered a previously unknown enzyme belonging to a new clade of sesquiterpene synthases that produces a terpene with a unique spiro-tricyclic scaffold. These findings contribute to the diversity of terpene scaffolds and mushroom terpene synthases, and have valuable applications in biotechnology.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Ching-Ning Huang, Xiaohui Lim, Leonard Ong, Chinchin Lim, Xixian Chen, Congqiang Zhang
Summary: This study successfully increased the yield of α-ionone by overexpressing bottleneck enzyme CCD1 and re-engineering the pathway. However, during scale-up, excessive overexpression of CCD1 led to a decrease in α-ionone production due to excessive hydrogen peroxide production. By overexpressing another enzyme, the oxidative stress was reduced and α-ionone yield was improved. This study provides a new strategy for improving strain robustness and microbial production of α-ionone, and may inspire the biosynthesis of other high-value compounds.
MICROBIAL CELL FACTORIES
(2022)
Article
Multidisciplinary Sciences
Xixian Chen, T. Rehka, Jeremy Esque, Congqiang Zhang, Sudha Shukal, Chin Chin Lim, Leonard Ong, Derek Smith, Isabelle Andre
Summary: Metabolic engineering is an attractive approach for the efficient production of natural products, but establishing biosynthetic pathways is crucial. The use of retrobiosynthetic pathway design with promiscuous enzymes offers an alternative solution to the challenge of incomplete native biochemical pathways.
NATURE COMMUNICATIONS
(2022)
Review
Biotechnology & Applied Microbiology
Xinyi Zhang, Xun Wang, Yu Zhang, Fei Wang, Congqiang Zhang, Xun Li
Summary: This review article summarizes the properties and functions of various iso-pentenyl phosphate kinases (IPKs), as well as novel IPP/DMAPP synthesis pathways involving IPKs and their applications in terpenoid biosynthesis. Furthermore, the authors discuss strategies to exploit novel pathways and unleash their potential for terpenoid biosynthesis.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Agriculture, Multidisciplinary
Thomas Lautier, Derek J. Smith, Lay Kien Yang, Xixian Chen, Congqiang Zhang, Gilles Truan, Nic D. Lindley
Summary: Cytochromes P450, a superfamily of monooxygenases, have versatile substrate specificity. Metabolic engineering can exploit this feature to unlock new metabolic pathways. However, expressing cytochromes P450 in a different host can be challenging. This study focused on optimizing the in vivo activity of CYP97H1 in Escherichia coli to produce fi-cryptoxanthin, a difficult carotenoid intermediate. Through engineering the N-terminal region of CYP97H1, identifying compatible redox partners, defining the optimal cellular background, and adjusting culture and induction conditions, the production of fi-cryptoxanthin increased by 400 times compared to the initial strain, reaching 2.7 mg/L and accounting for 20% of total carotenoid production.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Nicola Tan, Leonard Ong, Sudha Shukal, Xixian Chen, Congqiang Zhang
Summary: This study screened various nerolidol synthases from bacteria, fungi, and plants and found that the strawberry nerolidol synthase was most active in Escherichia coli. Through systematic optimization of the biosynthetic pathways, carbon sources, inducer, and genome editing, the researchers constructed a series of deletion strains that produced high yields of 100% trans-nerolidol. The results of this study lay the foundation for the industrial production of nerolidol and inspire the biosynthesis of other isoprenoids.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Physical
T. Rehka, Deepti Sharma, Fu Lin, Yeu Khai Choong, Chinchin Lim, Chacko Jobichen, Congqiang Zhang
Summary: The crystal structure of Agrocybe pediades linalool synthase (Ap.LS) was determined, revealing that its specificity is determined by the region of 60-69aa and Tyr299. Mutants of Ap.LS Y299 produced long-chain products. It was also found that microbial terpene synthases with asparagine at a specific position mainly produce cyclized products, while those with a bulky tyrosine produce linear products.
Article
Biochemistry & Molecular Biology
Thomas Lautier, Derek J. Smith, Lay Kien Yang, Xixian Chen, Congqiang Zhang, Gilles Truan, Nic D. Lindley
Summary: Molecular biodiversity is a result of enzymatic regioselectivities in branched metabolic pathways. Metabolites with internal structural symmetry, such as beta-carotene, offer identical extremities to enzymes, presenting additional complexity. This study investigates the unique monohydroxylase activity of CYP97H1, the only monohydroxylase among CYP97 dihydroxylases, in a substrate with two identical sites for hydroxylation. It is found that the N-terminal globular domain of CYP97H1, which contains a hydrophobic patch at the entrance of the substrate channel, is responsible for this regioselectivity.
Article
Biotechnology & Applied Microbiology
Aurelie Bouin, Congqiang Zhang, Nic D. Lindley, Gilles Truan, Thomas Lautier
Summary: Fusion of catalytic domains can enhance cascade reactions, but designing a suitable fusion protein and choosing an appropriate linker is challenging. To study the impact of linker parameters on fusion proteins, a library of various linkers was created. Fusion proteins were obtained by fusing lycopene cyclase (crtY) and beta-carotene hydroxylase (crtZ) using the linkers, and their efficiency was evaluated. The results showed that in addition to enzyme orientation and linker size, the first amino acid of the linker plays a crucial role in determining fusion protein efficiency. The diverse linker library can be applied to fine-tune fusion proteins with other enzyme pairs.
METABOLIC ENGINEERING COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Xixian Chen, Xiaohui Lim, Aurelie Bouin, Thomas Lautier, Congqiang Zhang
Summary: The study demonstrated the microbial biosynthesis of glycosylated carotenoids in Escherichia coli through metabolic engineering, significantly improving their water solubility and bioavailability. By fine-tuning the carotenoid-biosynthetic genes, different kinds of carotenoid glucosides were successfully produced.
BIORESOURCES AND BIOPROCESSING
(2021)