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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2017

Temperature selection drives evolution of function-valued traits in a marine diatom

Rapid evolution in response to environmental change will likely be a driving force determining the distribution of species and the structure of communities across the biosphere in coming decades. This is especially true of microorganisms, many of which may be able to evolve in step with rising temperatures. An ecologically indispensable group of microorganisms with great potential for rapid thermal adaptation are the phytoplankton, the diverse photosynthetic microbes forming the foundation of most aquatic food webs. We tested the capacity of a globally important phytoplankton species, the marine diatom Thalassiosira pseudonana, for rapid evolution in response to temperature. Evolution of replicate populations at 16 and 31{degrees}C for 350-450 generations led to significant divergence in several traits associated with T. pseudonanas thermal reaction norm (TRN) for per-capita population growth, as well as in its competitive ability for nitrogen (commonly limiting in marine systems). Of particular interest were evolution of the optimum temperature for growth, the upper critical temperature, and the derivative of the TRN, an indicator of potential tradeoffs resulting from local adaptation to temperature. This study offers a broad examination of the evolution of the thermal reaction norm and how modes of TRN variation may govern a populations long-term physiological, ecological, and biogeographic response to global climate change.

evolutionary biology↗

bioRxiv2017

Metabolism constrains bird and mammal ranges and predicts shifts in response to climate change

AimWe test whether physiological constraints on maximum metabolic rate and the factor by which endotherms can elevate their metabolism (metabolic expansibility) govern cold range limits for mammal and bird species.\n\nLocationGlobal\n\nMethodsWe examine metabolic expansibility at the cold range boundary (MEO_SCPLOWCRBC_SCPLOW) and its trait predictors and then use MEO_SCPLOWCRBC_SCPLOW to project range shifts for 210 mammal and 61 bird species.\n\nResultsWe find evidence for metabolic constraints: the distributions of metabolic expansibility at the cold range boundary peak at similar values for birds (2.7) and mammals (3.2). The right skewed distributions suggest some species have adapted to elevate or evade metabolic constraints. Mammals exhibit greater skew than birds, consistent with their diverse thermoregulatory adaptations and behaviors. Mammal and bird species that are small and occupy low trophic levels exhibit high levels of MEO_SCPLOWCRBC_SCPLOW. Mammals with high MEO_SCPLOWCRBC_SCPLOW tend to hibernate or use torpor. Predicted metabolic rates at the cold range boundaries represent large energetic expenditures (>50% of maximum metabolic rates). We project species to shift their cold range boundaries poleward by an average of 3.9{degrees} latitude by 2070.\n\nMain conclusionsOur analysis suggests that metabolic constraints provide a viable mechanism for projecting cold range boundaries and range shifts in response to climate change for endotherms.

ecology↗

bioRxiv2017

Modeling mesoscopic cortical dynamics using a mean-field model of conductance-based networks of adaptive exponential integrate-and-fire neurons

Voltage-sensitive dye imaging (VSDi) has revealed fundamental properties of neocortical processing at macroscopic scales. Since for each pixel VSDi signals report the average membrane potential over hundreds of neurons, it seems natural to use a mean-field formalism to model such signals. Here, we present a mean-field model of networks of Adaptive Exponential (AdEx) integrate-and-fire neurons, with conductance-based synaptic interactions. We study here a network of regular-spiking (RS) excitatory neurons and fast-spiking (FS) inhibitory neurons. We use a Master Equation formalism, together with a semi-analytic approach to the transfer function of AdEx neurons to describe the average dynamics of the coupled populations. We compare the predictions of this mean-field model to simulated networks of RS-FS cells, first at the level of the spontaneous activity of the network, which is well predicted by the analytical description. Second, we investigate the response of the network to time-varying external input, and show that the mean-field model predicts the response time course of the population. Finally, to model VSDi signals, we consider a one-dimensional ring model made of interconnected RS-FS mean-field units. We found that this model can reproduce the spatio-temporal patterns seen in VSDi of awake monkey visual cortex as a response to local and transient visual stimuli. Conversely, we show that the model allows one to infer physiological parameters from the experimentally-recorded spatio-temporal patterns.

neuroscience↗

bioRxiv2017

A GAL80 collection to nullify transgenes in Drosophila olfactory sensory neurons

Fruit flies recognize hundreds of ecologically relevant odors and respond appropriately to them. The complexity, redundancy and interconnectedness of the olfactory machinery complicate efforts to pinpoint the functional contributions of any component neuron or receptor to behavior. Some contributions can only be elucidated in flies that carry multiple mutations and transgenes, but the production of such flies is currently labor-intensive and time-consuming. Here, we describe a set of transgenic flies that express the Saccharomyces cerevisiae GAL80 in specific olfactory sensory neurons (OrX-GAL80s). The GAL80s effectively and specifically subtract the activities of GAL4-driven transgenes that impart anatomical and physiological phenotypes. OrX-GAL80s can allow researchers to efficiently activate only one or a few types of functional neurons in an otherwise nonfunctional olfactory background. Such experiments will improve our understanding of the mechanistic connections between odorant inputs and behavioral outputs at the resolution of only a few functional neurons.

neuroscience↗

bioRxiv2017

Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN

Renin-angiotensin system (RAS) is associated to peripheral fluid homeostasis and cardiovascular function, but recent evidence has also drawn its functional role in the brain. RAS has been described to regulate physiological and behavioral parameters related to stress response, including depressive symptoms. Apparently, RAS can modulate levels of brain derived neurotrophic factor (BDNF) and TRKB, which are important to neurobiology of depression and antidepressant action. However, interaction between BDNF/TRKB system and RAS in models predictive of antidepressant effect has not been investigated before. Accordingly, in the forced swimming test, we observed an antidepressant-like effect of systemic losartan but not with captopril or enalapril treament. Moreover, infusion of losartan into ventral hippocampus (vHC) and prelimbic prefrontal cortex (PL) mimicked the consequences of systemically injected losartan, whereas K252a, a blocker of TRK, infused into these brain areas impaired such effect. PD123319, an antagonist of AT2 receptor (AGTR2), infused into PL but not into vHC, also prevented systemic losartan effect. Cultured cortical cells of rat embryos indicate that angiotensin II (ANG2), possibly through AGTR2, increases the surface levels of TRKB, and favors its coupling to FYN, a SRC family kinase. The higher levels of agtr2 in cortical cells were decreased after insult with glutamate, and under this condition an interaction between losartan and ANG2 was achieved. Occurrence of TRKB/AGTR2 heterodimers was also observed, in MG87 cells GFP-tagged AGTR2 co-immunoprecipitated with TRKB. Therefore, antidepressant-like effect of losartan is proposed to occur through a shift of ANG2 binding towards AGTR2, followed by coupling of TRK/FYN and putative TRKB transactivation. Thus, AGTR1 show therapeutic potential as novel antidepressant therapy.

pharmacology and toxicology↗

bioRxiv2017

Experience-dependent translational state defined by cell type-specific ribosome profiling

Experience-dependent neuronal activity regulates the translation of mRNA, supporting memory formation. We have developed a new method termed translating ribosome affinity purification and ribosome profiling (TRiP) which allows us to determine cell type-specific ribosome occupancy of mRNA with nucleotide resolution. Using TRiP we show that a memory-inducing experience creates a distinct translational state in mouse CA1 pyramidal cells. The experience-dependent translation state is characterized by enhanced translation of protein-coding open reading frames (ORFs) including numerous components of the actin cytoskeleton and calcium/calmodulin binding proteins, and by decreased translation of a defined subset of genes containing upstream ORFs (uORFs). Using animals heterozygous for an unphosphorylatable allele of the eukaryotic translation initiation factor 2 (eIF2), we show that dephosphorylation of eIF2 contributes significantly to the experience-dependent translation state. These observations demonstrate that TRiP is a valuable methodology for studying physiologically relevant changes in translational state in genetically defined cell types.

genomics↗

bioRxiv2017

Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility

Summary StatementWe present a new image analysis technique using image velocimetry and spectral analysis that returns quantitative measures of gut contraction strength, frequency, and wave speed that can be used to study gut motility and other cellular movements.\n\nAbstractNormal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Whereas previous image analysis approaches have successfully extracted properties related to temporal frequency of motility modes, robust measures of contraction magnitude remain elusive. We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motions. We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild-types. Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.

developmental biology↗

bioRxiv2017

Towards an Unconscious Neurotherapy for Common Fears

Can evolutionarily hardwired fear responses, e.g. for spiders and snakes, be reprogramed unconsciously in the human brain? Currently, exposure therapy is amongst the most effective treatments for anxiety disorders1, but this intervention is subjectively aversive to patients, and rates of premature attrition from treatment have been reported to be as high as 70%2. Here we introduce a novel method to bypass the subjective unpleasantness in conscious exposure, by directly pairing monetary reward with unconscious occurrences of decoded representations of naturally feared objects in the brain. The typical way to identify multivoxel functional magnetic resonance imaging (fMRI) representations for feared objects involves repeated presentations of the relevant images explicitly to subjects. However, for our potential treatment method to be effective in actual clinical settings, we need to decode fear representations without triggering excessively aversive reactions which may cause patients to dropout from treatments prematurely. Here we overcome this challenge by capitalizing on recent advancements in fMRI decoding techniques: We employed a method called hyperalignment3,4 to infer the relevant representations of feared objects for a designated participant based on data from other surrogate participants. This way the procedure completely bypasses the need for the conscious encountering of feared objects. We demonstrate that our method can lead to reliable reductions in physiological fear responses measured by skin conductance as well as amygdala hemodynamic activity. Not only do these results raise the intriguing possibility that naturally occurring fear can be re-programmed outside of conscious awareness, importantly they also created the rare opportunity for a psychological intervention of this nature to be tested rigorously in a double-blind placebo-controlled fashion. This may pave the way for a novel treatment method, combining the appealing rationale and proven efficacy of conventional psychotherapy with the rigor and leverage of clinical neuroscience.

neuroscience↗

bioRxiv2017

Maize leaf functional responses to drought episode and rewatering

Effects of crop growth and physiological activity to drought and irrigation regimes have been extensively studied; however, the responses of plant growth, morphological and photosynthetic behaviors to drought episodes and thereafter rewatering receive a less attention. This field experiment was carried out directly in situ at an agricultural ecosystem research station during 2015-2016, in a northeastern China, on the renowned northeastern maize production belt, where is being threatened by severe drought. A field automatic rain-shelter was used, and five irrigation regimes including control, four drought episodes, and rewatering treatments were established. The chlorophyll contents (SPAD values), light-saturated photosynthetic rate (Asat), and photosystem II actual quantum yield ({Phi}PSII), maximum quantum yield (Fv'/Fm') decreased at lower leaf positions and with plant development. Episodic drought effects on plant growth, leaf morphological traits and photosynthetic processes at both vegetative and reproductive stages were severely remarked, particularly at late development stage and with longer drought duration. The recovery of leaf functional traits of the plants experienced historical-drought following re-irrigating was not fully restored to the level of the plants subjected to ample and normal water status; and the strength of recovery was proportional to the persistence of pre-drought episodes. The relationship of Asat with SPAD depends on water status and plant development. A principal component analysis can well denote the change patterns in responses to water status treatments with plant development. The results may give an insight into how to understand the maize traits responses to drought episode and rewatering, and this also might assist the drought-stricken crops to cope with future climatic change.

plant biology↗

bioRxiv2017

Inferring proteome dynamics during yeast cell cycle using gene expression data

Protein levels are most relevant physiologically, but measuring them genome-wide remains a challenge. In contrast, mRNA levels are much easier and less expensive to measure globally. Therefore, RNA levels are typically used to infer the corresponding protein levels. The steady-state condition (assumption that protein levels remain constant) is typically used to calculate protein abundances, as it is mathematically very convenient, even though it is often clear that it is not satisfied for proteins of interest. Here, we propose a simple, yet very effective, method to estimate genome wide protein abundances, which does not require the assumption that protein levels remain constant, and thus allows us to also predict proteome dynamics. Instead, we assume that the system returns to the baseline at the end of experiments; such an assumption is satisfied in many time-course experiments and in all periodic conditions (e.g. cell cycle). The approach only requires availability of gene expression and protein half-life data. As proof-of-concept, we calculated the predicted proteome dynamics for the budding yeast proteome during the cell cycle, which can be conveniently browsed online. The approach was validated experimentally by verifying that the predicted protein concentration changes were consistent with measurements for all proteins tested. Additionally, if proteomic data are also available, our approach can be used to predict how half-lives change in response to posttranslational regulation. We illustrated this application of our method with de novo prediction of changes in the degradation rate of Clb2 in response to post-translational modifications. The predicted changes were consistent with earlier observations in the literature.

bioinformatics↗

bioRxiv2017

Microbial-host metabolic systems interactions and the gut-brain axis: protective effects of microbial propionate upon the blood-brain barrier

Gut microbiome composition and function are symbiotically linked with host health, and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognized mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesized interactions between circulating gut-derived microbial metabolites and the blood-brain barrier (BBB) also contribute to the gut-brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed. After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 M) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signaling. Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut-brain axis that warrants further attention.

neuroscience↗

bioRxiv2017

The Epstein-Barr Virus miR-BHRF1 microRNAs Regulate Viral Gene Expression in cis

The Epstein-Barr virus (EBV) miR-BHRF1 microRNA (miRNA) cluster has been shown to facilitate B-cell transformation and promote the rapid growth of the resultant lymphoblastoid cell lines (LCLs). However, we find that expression of physiological levels of the miR-BHRF1 miRNAs in LCLs transformed with a miR-BHRF1 null mutant ({triangleup}123) fails to increase their growth rate. We demonstrate that the pri-miR-BHRF1-2 and 1-3 stem-loops are present in the 3UTR of transcripts encoding EBNA-LP and that excision of pre-miR-BHRF1-2 and 1-3 by Drosha destabilizes these mRNAs and reduces expression of the encoded protein. Therefore, mutational inactivation of primiR-BHRF1-2 and 1-3 in the {triangleup}123 mutant upregulates the expression of not only EBNA-LP but also EBNA-LP-regulated mRNAs and proteins, including LMP1. We hypothesize that this overexpression causes the reduced transformation capacity of the {triangleup}123 EBV mutant. Thus, in addition to regulating cellular mRNAs in trans, miR-BHRF1-2 and 1-3 also regulate EBNA-LP mRNA expression in cis.\n\nHighlightsO_LIThe EBV miR-BHRF1 microRNAs do not up upregulate B cell growth in trans.\nC_LIO_LIEBNA-LP expression is downregulated by pri-miR-BHRF1-2 and 1-3 acting in cis.\nC_LIO_LILoss of miR-BHRF1-2 and 1-3 causes EBNA-LP overexpression and inhibits B cell growth.\nC_LIO_LINovel alternative splicing of EBV Cp/Wp transcripts was identified.\nC_LI

microbiology↗

bioRxiv2017

A novel unbiased test for molecular convergent evolution and discoveries in echolocating, aquatic and high-altitude mammals

Distantly related species entering similar biological niches often adapt by evolving similar morphological and physiological characters. The extent to which genomic molecular convergence, and the extent to which coding mutations underlie this convergent phenotypic evolution remain unknown. Using a novel test, we ask which group of functionally coherent genes is most affected by convergent amino acid substitutions between phenotypically convergent lineages. This most affected sets reveals 75 novel coding convergences in important genes that pattern a highly adapted organ: the cochlea, skin and lung in echolocating, aquatic and high-altitude mammals, respectively. Our test explicitly requires the enriched converged term to not be simultaneously enriched for divergent mutations, and correctly dismisses relaxation-based signals, such as those produced by vision genes in subterranean mammals. This novel test can be readily applied to birds, fish, flies, worms etc., to discover more of the fascinating contribution of protein coding convergence to phenotype convergence.

evolutionary biology↗

bioRxiv2017

QuimP - Analyzing transmembrane signalling in highly deformable cells

SummaryTransmembrane signalling plays important physiological roles, with G protein-coupled cell surface receptors being particularly important therapeutic targets. Fluorescent proteins are widely used to study signalling, but the analysis of image time series can be challenging, in particular when changes in cell shape are involved. To this end we have developed QuimP software. QuimP semi-automatically tracks cell outlines, quantifies spatio-temporal patterns of fluorescence at the cell membrane, and tracks local shape deformations. QuimP is particularly useful for studying cell motility, for example in immune or cancer cells.\n\nAvailability and ImplementationQuimP (http://warwick.ac.uk/quimp) consists of a set of Java plugins for Fiji/ImageJ (http://fiji.sc/) and can be easily installed through the Fiji Updater (http://warwick.ac.uk/quimp/wiki-pages/installation). It is compatible with Mac, Windows and Unix-based operating systems, requiring version >1.45 of Fiji/ImageJ and Java 8. QuimP is released as open source (https://github.com/CellDynamics/QuimP/) under an academic licence.\n\nContactT.Bretschneider@warwick.ac.uk\n\nSupplementary InformationSupplementary materials (SI-A to SI-D) are available at Bioinformatics online. Test data is available from http://warwick.ac.uk/quimp/test_data.

bioinformatics↗

bioRxiv2017

Lessons in effector and NLR biology of plant-microbe systems

A diversity of plant-associated organisms secrete effectors--proteins and metabolites that modulate plant physiology to favor host infection and colonization. However, effectors can also activate plant immune receptors, notably nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins, enabling plants to fight off invading organisms. This interplay between effectors, their host targets, and the matching immune receptors is shaped by intricate molecular mechanisms and exceptionally dynamic coevolution. In this article, we focus on three effectors, AVR-Pik, AVR-Pia, and AVR-Pii, from the rice blast fungus Magnaporthe oryzae (syn. Pyricularia oryzae), and their corresponding rice NLR immune receptors, Pik, Pia, and Pii, to highlight general concepts of plant-microbe interactions. We draw 12 lessons in effector and NLR biology that have emerged from studying these three little effectors and are broadly applicable to other plant-microbe systems.

plant biology↗

bioRxiv2017

OptoGap: an optogenetics-enabled assay for quantification of cell-cell coupling in multicellular cardiac tissue

Intercellular electrical coupling is an essential means of communication between cells. It is important to obtain quantitative knowledge of such coupling between cardiomyocytes and nonexcitable cells when, for example, pathological electrical coupling between myofibroblasts and cardiomyocytes yields increased arrhythmia risk or during the integration of donor (e.g. cardiac progenitor) cells with native cardiomyocytes in cell-therapy approaches. Currently, there is no direct method for assessing heterocellular coupling within multicellular tissue. Here we demonstrate experimentally and computationally a new contactless assay for electrical coupling, OptoGap, based on selective illumination of inexcitable cells that express optogenetic actuators and optical sensing of the response of coupled excitable cells, e.g. cardiomyocytes, that are light-insensitive. Cell-cell coupling is quantified by the energy required to elicit an action potential via junctional current from the light-stimulated cell(s). The proposed technique is experimentally validated against the standard indirect approach, GapFRAP, using light-sensitive cardiac fibroblasts and non-transformed cardiomyocytes in a two-dimensional setting. Its potential applicability to the complex three-dimensional setting of the native heart is corroborated by computational modeling and proper calibration.\n\nIntercellular coupling is a fundamental form of communication between cells, essential for the synchronization of physiological processes in different organs. Pathologically altered coupling or the emergence of de novo coupling between native and donor cells are problems of interest in many cardiac applications, e.g. during cell delivery and cell integration for cardiac repair therapy1,2. In particular, interactions between cardiomyocytes and fibroblasts are of interest, especially the pro-arrhythmic increase in coupling as the latter transition to myofibroblasts3-6.\n\nElectrical coupling in cardiac tissue is mediated primarily by low-resistance paths formed by gap-junctional proteins (connexins), that can link cardiomyocytes (CMs) to each other and to non-cardiomyocytes (nCMs), such as fibroblasts. Qualitative and quantitative methods, e.g. immunofluorescence, messenger RNA and Western blots, are often used to assay connexin expression levels as a surrogate measure of coupling, but they do not provide functional information. A method for direct quantification of cell-cell coupling within the multicellular tissue context is highly desirable.

bioengineering↗

bioRxiv2017

Quantitative DSB sequencing (qDSB-Seq): a method for genome-wide accurate estimation of absolute DNA double-strand break frequencies per cell

Sequencing-based methods for mapping DNA double-strand breaks (DSBs) allow measurement only of relative frequencies of DSBs between loci, which limits our understanding of the physiological relevance of detected DSBs. We propose quantitative DSB sequencing (qDSB-Seq), a method providing both DSB frequencies per cell and their precise genomic coordinates. We induced spike-in DSBs by a site-specific endonuclease and used them to quantify labeled DSBs (e.g. using i-BLESS). Utilizing qDSB-Seq, we determined numbers of DSBs induced by a radiomimetic drug and various forms of replication stress, and revealed several orders of magnitude differences in DSB frequencies. We also measured for the first time Top1-dependent absolute DSB frequencies at replication fork barriers. qDSB-Seq is compatible with various DSB labeling methods in different organisms and allows accurate comparisons of absolute DSB frequencies across samples.

genomics↗

bioRxiv2017

The Novel Monocomponent FAD-dependent Monooxygenase HpaM Catalyzes the 2-Decarboxylative Hydroxylation of 5-Hydroxypicolinic Acid in Alcaligenes faecalis JQ135

5-hydroxypicolinic acid (5HPA) is a natural pyridine derivative that can be microbially degraded. However, the physiological, biochemical, and genetic foundation of the microbial catabolism of 5HPA remains unknown. In this study, a gene cluster hpa (which is involved in degradation of 5HPA in Alcaligenes faecalis JQ135) was cloned and HpaM was identified as a novel monocomponent FAD-dependent monooxygenase. HpaM shared a sequence only 31% similarity with the most related protein 6-hydroxynicotinate 3-monooxygenase (NicC) of Pseudomonas putida KT2440. hpaM was heterologously expressed in E. coli BL21(DE3), and the recombinant HpaM was purified via Ni-affinity chromatography. HpaM catalyzed the 2-decarboxylative hydroxylation of 5-HPA, thus generating 2,5-dihydroxypyridine (2,5-DPH). Monooxygenase activity was only detected in the presence of FAD and NADH, but not of FMN and NADPH. The apparent Km values of HpaM toward 5HPA and NADH were 45.4 and 37.8 , respectively. Results of gene deletion and complementation showed that hpaM was essential for 5HPA degradation in Alcaligenes faecalis JQ135.\n\nImportancePyridine derivatives are ubiquitous in nature and important chemical materials that are currently widely used in agriculture, pharmaceutical, and chemical industries. Thus, the microbial degradation and transformation mechanisms of pyridine derivatives received considerable attention. Decarboxylative hydroxylation was an important degradation process in pyridine derivatives, and previously reported decarboxylative hydroxylations happened in the C3 of the pyridine ring. In this study, we cloned the gene cluster hpa, which is responsible for 5HPA degradation in Alcaligenes faecalis JQ135, thus identifying a novel monocomponent FAD-dependent monooxygenase HpaM. Unlike 3-decarboxylative monooxygenases, HpaM catalyzed decarboxylative hydroxylation in the C2 of the pyridine ring in 5-hydroxypicolinic acid. These findings deepen our understanding of the molecular mechanism of microbial degradation of pyridine derivatives. Furthermore, HpaM offers potential for applications to transform useful pyridine derivatives.

microbiology↗