Article
Biology
Ranuka T. T. Hewage, Cheng-Chung Tseng, Suh-Yuen Liang, Chen-Yu Lai, Hsiao-Ching Lin
Summary: Two new derivatives were discovered, which can serve as important drugs and bioactive substances. In addition, two auxiliary enzymes were found to generate structurally diverse bisabolene compounds. There are numerous potential applications for these structurally diverse derivatives.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Rong Chen, Qidong Jia, Xin Mu, Ben Hu, Xiang Sun, Zixin Deng, Feng Chen, Guangkai Bian, Tiangang Liu
Summary: Chimeric terpene synthases unique to fungi produce structurally diverse di-and sesterterpenes. The origin and evolution of PTTS genes in Dikarya were explored, suggesting an early gene duplication event and frequent gene loss among subsequent lineages. Biochemical characterization of 74 PTTS genes revealed 34 active enzymes producing 24 terpenes, including previously unknown sesterterpenes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Nikolai A. Loehr, Frederic Eisen, Wiebke Thiele, Lukas Platz, Jonas Motter, Wolfgang Huettel, Markus Gressler, Michael Mueller, Dirk Hoffmeister
Summary: This study describes an unprecedented class of non-reducing polyketide synthases (NR-PKS) that can synthesize octaketide pigments. The researchers identified CoPKS1 and CoPKS4 of the mushroom genus Cortinarius as new atrochrysone carboxylic acid synthases. These findings illustrate how the biosynthesis of bioactive metabolites evolved independently in different groups of organisms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Baofu Xu, Dean J. Tantillo, Jeffrey D. Rudolf
Summary: The study investigated the mechanism of the first diterpene synthase known to form the eunicellane skeleton, highlighting the importance of D94 and E169 in the process. Bnd4 was found to have unique sesquiterpene cyclase activity and the ability to prenylate small molecules, demonstrating its versatility in natural product biosynthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Shuang He Liu, Jia Li Sun, Yi Ling Hu, Li Zhang, Xuan Zhang, Zhang Yuan Yan, Xing Guo, Zhi Kai Guo, Rui Hua Jiao, Bo Zhang, Ren Xiang Tan, Hui Ming Ge
Summary: This study reveals the biosynthesis pathway of Sordarin and uncovers a novel strategy for the formation of the rearranged diterpene skeleton.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Zhiyi Zhou, Jianchun Xian, Wuke Wei, Chong Xu, Jinfen Yang, Ruoting Zhan, Dongming Ma
Summary: This study compared the composition and quantity of terpenoids in different parts of Chrysanthemum indicum through volatile metabolic profiling, identifying various monoterpenoids and sesquiterpenoids. Additionally, two monoterpene synthases and two sesquiterpene synthases highly expressed in the root were cloned using transcriptome data. These findings offer insights into the bioactive compounds' composition, formation, and regulation.
Review
Microbiology
Birgit Piechulla, Chi Zhang, Daniela Eisenschmidt-Boenn, Feng Chen, Nancy Magnus
Summary: The 'biogenetic isoprene rule' proposed in the mid 20th century outlined the biosynthesis of terpenoids through the polymerization of C-5 isoprene units; the discovery of IDMTs has revealed a novel pathway for irregular terpene biosynthesis; this new route showcases nature's creativity in generating chemical diversity for organismal fitness, particularly in terpenoids.
FEMS MICROBIOLOGY REVIEWS
(2021)
Review
Biochemistry & Molecular Biology
Nicole G. H. Leferink, Nigel S. Scrutton
Summary: Terpenoids are natural products with significant industrial interest, and engineered microbes are increasingly being used to produce them. Terpene synthases play a crucial role in the structural diversity of natural terpenoids, but lack a strong sequence-function relationship, making product-outcome predictions challenging. New advances in genome mining, computational modeling, high-throughput screening, and machine-learning are expected to allow more predictive engineering of these enzymes in the future.
Review
Plant Sciences
Yifan Jiang, Wanbo Zhang, Xinlu Chen, Weijiao Wang, Tobias G. Kollner, Sumei Chen, Fadi Chen, Feng Chen
Summary: This review examines the terpenoids produced by Chrysanthemum species, highlighting their diversity and specificity to certain varieties or species. The enzymes and genes involved in terpene biosynthesis pathways are described, with a particular focus on isoprenyl diphosphate synthases and terpene synthases. The potential biological functions of terpenoids in chemical defenses and the prospects for future research and applications are also discussed.
CRITICAL REVIEWS IN PLANT SCIENCES
(2021)
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
Agriculture, Multidisciplinary
Chun-Wei Chuang, Chi-Hsiang Wen, Tsai-Jung Wu, Ching-Ching Li, Nien-Ting Chiang, Li-Ting Ma, Chen-Lung Ho, Gene-Sheng Tung, Chin-Cheng Tien, Yi-Ru Lee, Fang-Hua Chu
Summary: Zanthoxylum ailanthoides is a traditional spice crop in Taiwan with unique smells and tastes that differ between prickly (young) and nonprickly (mature) leaves. Different volatile terpenes between prickly young and nonprickly mature leaves were identified and considered to be one of the sources of their aromas. The functions of terpene synthase genes were investigated, revealing the biosynthesis of compounds responsible for the distinct aromas of Z. ailanthoides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tzu-Ho Chen, Hsiao-Ching Lin
Summary: DTSs are important bioactive natural products found in various organisms, with diverse bioactivities including anti-bacterial, anti-fungal, anti-viral, and anti-cancer properties. Recently discovered DTS synthases can produce compounds with unique structures. This article summarizes the key features of these DTS synthases, including the chemical mechanisms, catalytic motifs, and functional domains involved.
Article
Biochemical Research Methods
Janani Durairaj, Elena Melillo, Harro J. Bouwmeester, Jules Beekwilder, Dick de Ridder, Aalt D. J. van Dijk
Summary: Predicting enzyme function is a challenging task, especially with the vast amount of protein sequences and limited experimental characterization. This study presents a computational approach using homology modeling, machine learning, and co-evolution analysis to predict carbocation specificity in sesquiterpene synthases. The results identify residues and structural regions influencing product specificity and can be applied to enzyme engineering in various enzyme classes.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Plant Sciences
Jun He, Francel Verstappen, Ao Jiao, Marcel Dicke, Harro J. Bouwmeester, Iris F. Kappers
Summary: Our study revealed the important roles of the TPS gene family in cucumber in response to different herbivores, with multiple CsTPS genes showing upregulation in leaves upon herbivory. The products generated by the expressed proteins matched the terpenoids recorded in the volatile blend released by herbivore-damaged leaves, providing detailed insights into the dynamics and fine-tuning of the emission of herbivore-induced plant volatiles in cucumber.
Article
Biochemistry & Molecular Biology
Shuyan Song, Ruitao Jin, Yufan Chen, Sitong He, Kui Li, Qian Tang, Qi Wang, Linjuan Wang, Mengjuan Kong, Natalia Dudareva, Brian J. Smith, Fei Zhou, Shan Lu
Summary: Terpenoids are the largest class of plant metabolites with diverse functions. The synthesis of terpenoids involves enzymes called geranylgeranyl diphosphate synthases (GGPPSs) and geranyl diphosphate synthases (GPPSs). Through phylogenetic analysis and experimental characterization, it was found that the expansion and functional divergence of GPPS genes started in nonvascular plants, leading to the evolution of both homomeric and heteromeric GPPSs. Mutagenesis and simulations revealed amino acid residues crucial for the functional divergence of GPPSs and GGPPSs.
Article
Biochemical Research Methods
Yichao Han, Fuzhong Zhang
PLOS COMPUTATIONAL BIOLOGY
(2020)
Review
Biotechnology & Applied Microbiology
Christopher J. Hartline, Alexander C. Schmitz, Yichao Han, Fuzhong Zhang
Summary: Metabolic engineering enables the production of valuable chemicals using microbial organisms, with dynamic metabolic engineering allowing cells to autonomously adjust flux in response to their metabolic state. The review discusses theoretical works, molecular mechanisms, and applications of dynamic control systems in improving metrics in metabolic engineering.
METABOLIC ENGINEERING
(2021)
Review
Biochemical Research Methods
Yichao Han, Fuzhong Zhang
CURRENT OPINION IN BIOTECHNOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Lukas Lauterbach, Anwei Hou, Jeroen S. Dickschat
Summary: The dauc-8-en-11-ol synthase from Streptomyces venezuelae was found to have increased catalytic activity towards alternative terpene precursors after aromatic amino acid residues at the enzyme surface were exchanged by site-directed mutagenesis. This led to a 4-fold increase in yield in preparative scale incubations, mainly due to enhanced enzyme stability rather than improved enzyme kinetics.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Anwei Hou, Bernd Goldfuss, Jeroen S. Dickschat
Summary: The reinvestigation of linalool synthase from Chryseobacterium polytrichastri revealed its diterpene synthase activity, leading to the discovery of new compounds with unique skeletons. Isotopic labeling experiments and DFT calculations were used to study the enzyme mechanism and explain the formation of an unusual ethyl group. Rational exchanges of active site residues resulted in major functional switches and the production of new compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Anwei Hou, Jeroen S. Dickschat
Summary: The study conducted site-directed mutagenesis experiments on the sesterterpene synthase SmTS1 from Streptomyces mobaraensis, revealing diverse effects of mutations on catalytic activity and enzyme function switch. Rational explanations were provided for these findings, offering insights into protein engineering of terpene synthases for improved efficiency or altered functions.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Anwei Hou, Jeroen S. Dickschat
Summary: Enzymatic conversion of four synthetic farnesyl diphosphate analogues with three bacterial sesquiterpene synthases resulted in the production of several previously unknown compounds, showcasing a new chemical space. Substrates with blocked or altered reactivities also provided insights into cyclisation mechanisms and the potential to catalyse reactions with different initial cyclisation modes.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Ying Duan, Marina Toplak, Anwei Hou, Nelson L. Brock, Jeroen S. Dickschat, Robin Teufel
Summary: The text discusses the biosynthesis and mechanism of action of bacterial tropone natural products, which are involved in various symbiotic interactions. The process involves phenylacetic acid catabolism and the enzyme TdaE, leading to the production of tropolone and other secondary metabolites such as tropodithietic acid.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Zhiyang Quan, Anwei Hou, Bernd Goldfuss, Jeroen S. Dickschat
Summary: The complex cyclisation mechanism of six compounds synthesized by the multiproduct chimeric sesterterpene synthase AcAS from Aspergillus calidoustus was investigated using experimental and computational methods. Protein engineering improved enzyme yields and expanded substrate scope.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Anwei Hou, Jeroen S. Dickschat
Summary: Isotopic labelling experiments were used to investigate the fragmentation mechanisms leading to the formation of pronounced fragment ions during EI mass spectrometry of the diterpene hydrocarbons polytrichastrene A and wanju-2,5-diene. Enzymatic synthesis of twenty singly C-13-labelled isotopomers of these diterpenes allowed for conclusions on the fragmentation mechanisms observed in mass spectrometric investigation.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Hui Tao, Lukas Lauterbach, Guangkai Bian, Rong Chen, Anwei Hou, Takahiro Mori, Shu Cheng, Ben Hu, Li Lu, Xin Mu, Min Li, Naruhiko Adachi, Masato Kawasaki, Toshio Moriya, Toshiya Senda, Xinghuan Wang, Zixin Deng, Ikuro Abe, Jeroen S. Dickschat, Tiangang Liu
Summary: In this study, two fungal chimeric class I triterpene synthases (TrTSs) were characterized, which represent the first examples of non-squalene-dependent triterpene biosynthesis. The cyclization mechanisms and catalytic mechanisms of these enzymes were investigated, providing detailed insights into triterpene biosynthesis. Additionally, a screening platform was developed to discover a new TrTS. These findings reveal a new enzymatic mechanism for triterpene biosynthesis and enhance our understanding of terpene biosynthesis in nature.
Article
Chemistry, Organic
Jin Liang, Amy T. Merrill, Croix J. Laconsay, Anwei Hou, Qingyu Pu, Jeroen S. Dickschat, Dean J. Tantillo, Qiang Wang, Reuben J. Peters
Summary: A barley diterpene synthase (HvKSL4) was found to produce (14S)-cleistantha-8,12-diene (1). The formation of this compound involves a series of complex rearrangements, which were elucidated through quantum chemical calculations and labeling studies.
Article
Chemistry, Organic
Binbin Gu, Anwei Hou, Jeroen S. Dickschat
Summary: Both enantiomers of 2-Me-LPP were synthesized and purified enantioselectively. (R)-2-Me-LPP was found to be the on-pathway intermediate in the enzymatic conversion with 2MIBS, while a minor formation of 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Anwei Hou, Jeroen S. Dickschat
Summary: In this review, the recent advances in the use of isotopically labelled compounds to investigate the biosynthesis of polyketides, non-ribosomally synthesised peptides, and their hybrids are discussed. The use of isotopes in elucidating their structures and investigating enzyme mechanisms is highlighted. Selected examples of biosynthetic pathways are presented to reveal the principles of the labelling experiments. The presented examples demonstrate that the application of isotopically labelled compounds is still state of the art and can provide valuable information for natural product biosynthesis.
NATURAL PRODUCT REPORTS
(2023)
Article
Multidisciplinary Sciences
Jingyao Li, Bojing Jiang, Xinyuan Chang, Han Yu, Yichao Han, Fuzhong Zhang
Summary: The authors have developed a method to enhance the strength of low molecular-weight protein materials by fusing intrinsically-disordered mussel foot protein fragments. This approach can be applied to a wide range of protein-based materials and has the potential to achieve high yields.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Nicolas Huber, Edgar Alberto Alcala-Orozco, Thomas Rexer, Udo Reichl, Steffen Klamt
Summary: Cell-free production systems are commonly used for synthesizing industrial chemicals and biopharmaceuticals. This study presents a model-based optimization framework for cell-free enzyme cascades, taking into account parameter uncertainties. The approach was exemplified using the synthesis of GDP-fucose, resulting in significant improvements in the process.
METABOLIC ENGINEERING
(2024)