Biology subjects

Begum, K.

Publications and source records attributed to Begum, K..

4 recordsLinked to original sources

bioRxiv2022

Genome-wide investigation of Cytochrome P450 superfamily of Aquilaria agallocha: association with terpenoids and phenylpropanoids biosynthesis

P450 superfamily (CYPs) has been known as contributors to the metabolites diversity and their promiscuous nature has led to the flexibility in substrate specificity and functional diversity. Current study was designed to investigate CYPs in the genome of an agarwood producing plant species named Aquilaria agallocha. Agarwood, the resinous fragrant wood with numerous phytochemicals, produced when an Aquilaria plant respond to wound and microbial infection. These chemicals are of great interest to industries ascribing it a high economic value. However, the pathways for the biosynthesis of these metabolites have not been studied in context of Aquilaria CYPs. We identified 136 A. agallocha CYP proteins from the genome, characterized and classified them into 8 clans and 38 families. Functional analysis unveiled their participation in terpenoids, phenolics, flavonoids and other valuable metabolites biosynthesis. Conserved motifs were detected and evolutionary analysis revealed duplicated and orthologous pairs. Potential members for the biosynthesis of sesquiterpenoids and phenylpropanoids reported in Aquilaria and agarwood were elucidated and validated through expression profiles in stress induced callus tissues and infected Aquilaria tress. This study provides a strong foundation for biochemical characterization of Aquilaria CYPs which will aid heterologous production of valuable phytochemicals and untangle molecular mechanism of agarwood formation.

plant biology↗

bioRxiv2022

PrePCI: A structure- and chemical similarity-informed database of predicted protein compound interactions

We describe the Predicting Protein Compound Interactions (PrePCI) database which comprises over 5 billion predicted interactions between nearly 7 million chemical compounds and 19,797 human proteins. PrePCI relies on a proteome-wide database of structural models based on both traditional modeling techniques and the AlphaFold Protein Structure Database. Sequence and structural similarity-based metrics are established between template proteins in the Protein Data Bank, T, that bind small molecules, C, and proteins in the models database, Q. When these metrics pass a sequence threshold value, it is assumed that C also binds to Q with a probability derived from machine learning. If the relationship is based on structure, this probability is based on a scoring function that measures the extent to which C is compatible with the binding site of Q as described in the LT-scanner algorithm. For every predicted complex derived in this way, chemical similarity based on the Tanimoto Coefficient identifies other small molecules that may bind to Q. A likelihood ratio for the binding of C to Q is obtained from naive Bayesian statistics. The PrePCI algorithm performs well under different validations. It can be queried by entering a UniProt ID for a protein and obtaining a list of compounds predicted to bind to it along with associated probabilities. Alternatively, entering an identifier for the compound outputs a list of proteins it is predicted to bind. Specific applications of the database are described and a strategy is introduced to use PrePCI as a first step in a docking screen.

systems biology↗

bioRxiv2020

Childhood location correlates with epigenetic age and methylation stability in British-Bangladeshi migrants

BackgroundMigration from one environment to another often causes marked changes in developmental conditions. Here we compare epigenetic ageing and stability of the epigenetic maintenance system among British-Bangladeshi women who grew up in Bangladesh (adult migrants), where there are higher pathogen loads and poorer health care, to second-generation Bangladeshis who grew up in the UK. In our previous studies of these migrants, those who spent their childhoods in Bangladesh also had lower levels of reproductive hormones and a shorter reproductive lifespan compared to those who grew up in the UK, suggesting life history trade-offs during development. In the present study, we hypothesised that women who grew up in Bangladesh would have i) an older epigenetic/biological age compared to the women with a childhood in the UK and ii) that differences in the pace of epigenetic ageing might also be reflected by altered stability of DNA methylation marks. ResultsIllumina EPIC array methylation data from buccal tissue was used to establish epigenetic age estimates from 15 adult migrants and 11 second-generation migrants, aged 18-35 years. Using residuals from linear regression of DNA methylation-based biological age (DNAm age) on the chronological age, the results showed significant differences (p=0.016) in epigenetic age estimates: women whose childhood was in Bangladesh are on average 6.02 ({+/-} 2.34) years older, than those who grew up in London. We further investigated the efficiency of the epigenetic maintenance system which purportedly is reflected by epigenetic clocks. Methylation states of CpGs at the LHCGR/LHR locus, which contributes to Horvaths multi tissue epigenetic clock were evaluated. Based on the Ratio of Concordance Preference (RCP) approach that uses double-stranded methylation data, we find that maintenance of epigenetic information is more stable in women who grew up in Bangladesh. ConclusionsThe work supports earlier findings that adverse childhood environments lead to phenotypic life history trade-offs. The data indicate that childhood environments can induce subtle changes to the epigenetic maintenance system that are detectable long after exposure occurred. The implication of such a finding warrants further investigation as it implies that a less flexible epigenetic memory system established early in life could reduce the capacity to respond to different environmental conditions in adult life.

genetics↗

bioRxiv2020

Early-life environment programs reproductive strategies through epigenetic regulation of SRD5A1

Reproductive function and duration of the reproductive life span are phenotypically plastic and programmed in response to the early-life environment. Such adaptive responses are described and rationalized in life history theory in the context of resource availability, but the molecular mechanisms responsible have remained enigmatic. In this study, we hypothesized that epigenetic modifications underlie adaptive reproductive strategies, and found distinct methylation patterns in buccal DNA of Bangladeshi women who grew up in Bangladesh or the UK. The later pubertal onset and lower ovarian reserve associated with Bangladeshi childhood was seen to correlate with more numerous childhood infections, so we adopted a mouse model of pre-pubertal colitis to mimic these conditions. These mice have a similarly-altered reproductive phenotype, which enabled us to determine its mechanistic basis. Several genes encoding proteins with known functions in follicle recruitment were differentially expressed in the mice ovaries, and were also differentially methylated in the womens buccal DNA. One of these, SRD5A1 which encodes the steroidogenic enzyme 5 reductase-1, was down-regulated in the mice ovaries and hyper methylated at the same putative transcriptional enhancer as in the womens DNA; the levels of methylation correlating with gene expression levels. Srd5a1 expression was down-regulated also in the hypothalamus where 5 reductase-1 catalyzes production of neurosteroids that regulate gonadotropin releasing hormone (GnRH). Chemical inhibition of this enzyme affected both GnRH synthesis and release, and resulted in delayed pubertal onset in vivo. The activity of 5 reductase-1 in hypothalamus and ovary and the sensitivity of SRD5A1 to epigenetic regulation attest to its role in directing long-term physiological strategies in response to environmental conditions. In the reproductive axis, this includes timing of pubertal onset, adult reproductive function and duration of the reproductive lifespan.

developmental biology↗