Article
Multidisciplinary Sciences
Chongyang Wang, Changshui Liu, Xiaochuan Zhu, Quancai Peng, Qingjun Ma
Summary: This study reveals the structural flexibility of Vibrio dual lipases/transferases and proposes a mechanism for tuning the catalytic site to explain enzyme promiscuity. Enzyme promiscuity, the ability to catalyze multiple substrates and reactions, is widely observed but poorly understood. The researchers discovered a flexible catalytic triad machinery in Vibrio dual lipase/transferase that can undergo conformational changes to facilitate substrate and catalytic promiscuity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ryan P. Campbell, A. Carl Whittington, Diego A. R. Zorio, Brian G. Miller
Summary: The recruitment of promiscuous enzymes is a key step in metabolic pathway evolution. However, the factors determining the preferential recruitment of certain enzymes over others are not well understood. Through adaptive evolution of a glucokinase-deficient E. coli strain, it was found that the least active enzyme, AlsK, was preferentially recruited, while the more active enzymes, NagK and Mak, were not recruited, indicating that catalytic activity alone does not determine evolutionary outcomes.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Michael Schmutzer, Andreas Wagner
Summary: Mistranslation is a common and significant source of nongenetic variation that can affect adaptive evolution in multiple ways. It flattens adaptive landscapes, increases genetic variation available to selection, renders some mutations nonneutral, and affects the fitness of different genotypes unequally. Despite increasing the incidence of epistasis, mistranslation can still lead to populations evolving higher fitness on rugged landscapes.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Chemistry, Multidisciplinary
Morito Sakuma, Shingo Honda, Hiroshi Ueno, Kazuhito V. Tabata, Kentaro Miyazaki, Nobuhiko Tokuriki, Hiroyuki Noji
Summary: Enzymes display heterogeneity in their conformational and functional states, which is crucial for the evolution of new functions. A single-molecule enzyme assay was used to analyze functional substates in wild-type and mutant alkaline phosphatase. Mutant enzymes exhibited significantly heterogeneous functional substates, while the wild-type enzyme showed a highly homogeneous substate. The degree of functional substates correlated with the improvement in promiscuous activities. The findings highlight the importance of functional substates in enzyme evolution.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Morito Sakuma, Shingo Honda, Hiroshi Ueno, Kazuhito V. Tabata, Kentaro Miyazaki, Nobuhiko Tokuriki, Hiroyuki Noji
Summary: Enzymes have inherent heterogeneity in their conformational and functional states, which is key to the evolution of new functions. Single-molecule enzyme assays allow direct observation of these multiple functional substates. We analyzed functional substates in wild-type and mutant Escherichia coli alkaline phosphatase and found that mutant enzymes exhibited significantly heterogeneous functional substates, while the wild-type enzyme showed a highly homogeneous substate. Our study provides comprehensive evidence that functional substates can be easily altered by mutations and that the evolution towards new catalytic activities may involve modulation of these substates.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Dave W. Anderson, Florian Baier, Gloria Yang, Nobuhiko Tokuriki
Summary: This study characterizes the catalytic activity of a recently evolved bacterial enzyme under various laboratory conditions, revealing that adaptive landscapes may shift due to genotype-by-environment interactions and environment-dependent epistasis, impacting the fitness of functional mutations.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Jian-Rong Dai, M. S. Jiang-Tao Sha, Min-Hua Zong, Ning Li
Summary: In this work, the horseradish peroxidase (HRP)-catalyzed aerobic oxidation of reduced nicotinamide cofactors (NADH) was reported. The oxidation was achieved at neutral and alkaline pH by using external amino acids (AAs). The presence of AAs promoted the formation of compound III and its decay back to the ground state. This method offers an alternative way to recycle NAD(P)(+) and has potential for HRP-catalyzed aerobic oxidations.
Article
Multidisciplinary Sciences
Gloria Gamiz-Arco, Luis I. Gutierrez-Rus, Valeria A. Risso, Beatriz Ibarra-Molero, Yosuke Hoshino, Dusan Petrovic, Jose Justicia, Juan Manuel Cuerva, Adrian Romero-Rivera, Burckhard Seelig, Jose A. Gavira, Shina C. L. Kamerlin, Eric A. Gaucher, Jose M. Sanchez-Ruiz
Summary: The study revealed that the ancestral glycosidase has enhanced conformational flexibility but a comparatively rigid core, with stable activity and optimal temperature for thermophilic family-1 glycosidases. Unlike modern glycosidases, the ancestral glycosidase binds heme tightly and stoichiometrically at a well-defined buried site. The binding of heme rigidifies the TIM-barrel structure and allosterically enhances catalysis.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Andreas Kunzendorf, Guangcai Xu, Mohammad Saifuddin, Thangavelu Saravanan, Gerrit J. Poelarends
Summary: In this study, an enzyme independent of cofactors was engineered for the enantioselective synthesis of cyclopropanes via nucleophilic addition, demonstrating high stereocontrol over both stereocenters. The results highlight the potential of promiscuous enzymes in expanding the biocatalytic repertoire for non-natural reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Yi Shuang Wang, Wan Zheng, Nan Jiang, Yun Xia Jin, Zi Kang Meng, Meng Xin Sun, Yu Liang Zong, Tong Xu, Jiapeng Zhu, Ren Xiang Tan
Summary: This study discovered a new class of enzymes called ChaP that can catalyze the deconstruction of intradiol-like o-quinones and release CO2. Experimental evidence showed that by mutating and replacing specific residues, the enzyme's reaction trajectory and regioselectivity can be altered. The results of this study highlight the catalytic versatility and enzymatic plasticity of VOC enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Christina Nutschel, Cristina Coscolin, Benoit David, Daniel Mulnaes, Manuel Ferrer, Karl-Erich Jaeger, Holger Gohlke
Summary: Understanding the molecular origin of observed promiscuity range in enzymes is crucial, with the study revealing that promiscuous esterases are less flexible, more thermostable, and have increased specific activity compared to specific ones. This research provides a new starting point for exploration in biotechnology and synthetic chemistry by screening esterase sequence space through rigidity analyses.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Andrew J. O'Donnell, Ruiqi Huang, Jessica J. Barboline, Todd J. Barkman
Summary: Resurrected ancient enzymes of the caffeine synthase shed light on how ancestral biosynthetic catalytic capabilities lead to the convergent evolution of similar biochemical pathways. It appears that modern-day pathways likely originated from ancestral pathways with different inferred flux, and the modern enzymes independently evolved via gene duplication with convergent catalytic characteristics differentiating multiple ancestral activities through mutations.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Chemistry, Physical
Jian Yang, Yunzhu Xiao, Yu Liu, Ru Li, Lijuan Long
Summary: The recruitment and rapid evolution of promiscuous catalysis led to a new efficient biocatalyst for organophosphrus remediation, with a 10,000-fold increase in methyl-parathion hydrolysis and broadened substrate specificity. Structural, kinetic, and computational comparisons identified the molecular basis for the enhanced catalysis and revealed how the mutations reshaped the substrate pocket for better access to catalytic machinery.
CATALYSIS SCIENCE & TECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jie Fan, Huomiao Ran, Peng-Lin Wei, Yuanyuan Li, Huan Liu, Shu-Ming Li, Youcai Hu, Wen-Bing Yin
Summary: The biosynthetic pathway of pretrichodermamide A (1) in Trichoderma hypoxylon involves multiple enzymes that generate diverse fungal epidithiodiketopiperazines (ETPs). The study identified seven tailoring enzymes encoded by the tda cluster, including P450s TdaB and TdaQ for 1,2-oxazine formation, TdaI for C7'-hydroxylation, TdaG for C4, C5-epoxidation, methyltransferases TdaH for C6'- and TdaO for C7'-O-methylation, and reductase TdaD for furan opening. Deletion of genes led to the discovery of 25 novel ETPs, indicating the catalytic promiscuity of Tda enzymes. This research uncovers a hidden library of ETP alkaloids and enhances our understanding of the chemical diversity of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Daniel Voros, Balazs Konnyu, Tamas Czaran
Summary: The author suggests the potential importance of catalytic promiscuity in early replicator communities. Computer simulations show that catalytic diversity may have played a significant role in supporting minimal metabolic processes necessary for the emergence of life.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)