Biology subjects

Harwani, D.

Publications and source records attributed to Harwani, D..

3 recordsLinked to original sources

bioRxiv2021

Comparative whole-genome analysis of a Thar desert strain Streptomyces sp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system

We sequenced the genome of Streptomyces sp. JB150, isolated from a unique site of the Thar desert in India. Genome mining of the JB150 genome revealed the presence of many interesting secondary metabolic biosynthetic gene clusters (BGCs). The encoded parvome of JB150 includes non-ribosomal peptides, polyketides including {beta}-lactone, butyrolactone, ectoine, lantipeptides, lasso peptides, melanin, resorcinol, siderophores, terpenoids, thiopeptides, and other types of hybrid compounds. Among them, ~30% BGCs displayed a high degree of novelty. The genome of JB150 was enriched for a large assortment of specialized genes coding for the production of many interesting biomolecules comprising compatible solutes, multiple stress-response regulators, transport proteins, protein secretion systems, signaling molecules, chaperones and storage reserves, etc. The presence of diverse members of CAZymes enzyme families, high numbers of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), trehalose and aromatic compounds synthesis genes, putative orthologues to several of the classical fatty acid synthesis components, prototrophy for many essential amino acids exhibit metabolic versatility of JB150 to inhabit in the extreme desert environment. Besides, the genome of JB150 was observed to specifically encode thiazole-oxazole-modified thiazolemicrocin (TOMM) and ectoine. The comparison of the complete genomes of Streptomyces sp. JB150 and seven other actinomycete strains belonging to different desert ecosystems unveiled the presence of many previously undetected, distinctive, biological, and genomic signatures. We propose that these genetic traits endowed by these strains are essential for their adaptation in the highly underprivileged, extreme ecosystem of the Thar desert to cope with multiple abiotic stressors, oligotrophic nutrient conditions and to produce a huge repertoire of diverse secondary metabolites.

genomics↗

bioRxiv2021

In silico analysis and cluster validation of potential breast cancer nsSNPs of serological tumor marker CA27.29

Background & ObjectivesCA27.29 is a breast cancer-associated glycoprotein. Many genetic variations caused by non-synonymous nucleotide polymorphisms (nsSNPs) are known to affect the functionality of the CA27.29 protein. MethodsIn the present manuscript, an in silico analysis of the genetic variations in CA27.29 was done to observe functional nsSNPs that possibly alter its stability. Among 2205 SNPs identified from the publically available SNP database (dbSNP), 213 (9.66%) synonymous SNPs, 24 (1.09%) non-synonymous SNPs, and 1351 (61.27%) noncoding intronic SNPs were observed. The function predictability tools SIFT, Provean and Polyphen2 were used to uncover variations in the analyzed nsSNPs and their functionality. ResultsA total of 16, 20 and 10 non-synonymous SNPs (nsSNPs) were predicted to be damaging or deleterious by SIFT, Polyphen, and Provean tools respectively. Intriguingly, 9 nsSNPs were predicted to be damaging by all the three tools used while 4 nsSNPs were predicted to be damaging by SIFT and Polyphen tools. The substitutions C/G->T and G->A/T were observed to be dominant in the analyzed nsSNPs that probably have damaging role to CA27.29 glycoprotein. Moreover, the validation of results using ClinVar tool revealed that all the analyzed possibly, probably and highly damaging nsSNPs are yet to be reported and studied. Besides this, we found Global minor allele frequency (Global MAF) for only 11 nsSNPs, the values of which were observed to be <0.1% that further confirmed the novelty of the analyzed variants. Interpretation & ConclusionsAmong the analyzed nsSNPs, 3 nsSNPs rs145691584, rs148332231 and rs191544901 were found to be located in 3UTR region of CA27.29 gene that were assumed to have the possible functional roles in altering the protein stability. The present study is useful to gain useful insights into the genetic variations in nsSNPs that may playing a critical role in determining the susceptibility to breast cancer.

bioinformatics↗

bioRxiv2021

Adaptive laboratory evolution triggers pathogen-dependent broad-spectrum antimicrobial potency in Streptomyces

In the present study, adaptive laboratory evolution was used to stimulate antibiotic production in a weak antibiotic-producing Streptomyces strain JB140. The seven different competition experiments utilized three serial passages (three cycles of adaptation-selection of 15 days each) of a weak antibiotic-producing Streptomyces strain (wild-type) against one (biculture) or two (triculture) or three (quadriculture) target pathogens. This resulted in the evolution of a weak antibiotic-producing strain into the seven unique mutant phenotypes that acquired the ability to constitutively exhibit increased antimicrobial activity against bacterial pathogens. The mutant not only effectively inhibited the growth of the tested pathogens but also observed to produce antimicrobial against multidrug-resistant (MDR) E. coli. Intriguingly, the highest antimicrobial activity was registered with the Streptomyces mutants that were adaptively evolved against the three pathogens (quadriculture competition). In contrast to the adaptively evolved mutants, a weak antimicrobial activity was detected in the un-evolved, wild-type Streptomyces. To get molecular evidence of evolution, RAPD profiles of the wild-type Streptomyces and its evolved mutants were compared that revealed significant polymorphism among them. These results demonstrated that competition-based adaptive laboratory evolution method can constitute a platform for evolutionary engineering to select improved phenotypes (mutants) with increased production of antibiotics against targeted pathogens.

microbiology↗