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Biology subjects

Aslam, M. F.

Publications and source records attributed to Aslam, M. F..

3 recordsLinked to original sources

Analysis of genome sequences of marine isolates of Saccharomyces cerevisiae

Saccharomyces cerevisiae is the workhorse of the fermentation industry, as well as a dominant laboratory model organism and chassis for synthetic biology. The great majority of known isolates are from terrestrial sources, but a number of strains are reported to have been isolated from seawater and marine sediments and organisms. Marine strains may have superior tolerance to salt and fermentation inhibitors, and other properties which may be useful in industry, especially in processes based on seawater and marine biomass, as well as casting new light on the physiology and evolution of this species. We have recently reported the isolation of several marine strains of S. cerevisiae and comparisons with terrestrial strains for ethanol production. Here we describe the genome sequences of three marine S. cerevisiae strains, AZ65, AZ118 and AZ123. To the best of our knowledge, these are the first genome sequences of marine S. cerevisiae strains for which published isolation data are available. Superior salt and inhibitor tolerance of the strains, compared to multiple terrestrial and industrial comparators, was confirmed. Analysis of the ENA locus, believed to be related to salt tolerance in S. cerevisiae, did not show strong evidence for modification of copy number, protein sequence, or promoter sequence of this locus in response to a marine habitat. The physiological and genetic basis of salt and inhibitor tolerance thus remains to be determined.

microbiology↗

MTBP allosterically activates Cdk8-CycC kinase activity

How the approximately 300 human protein kinases identify their dedicated substrates despite the significant overlap of their phosphorylation consensus sequences is relevant for nearly all cellular processes. We show here that the Cdk8/19-CycC kinase uses mutually exclusive targeting and activation factors to facilitate distinct cellular roles. The Med12 protein is known to target Cdk8/19-CycC to the mediator of transcription complex to control the transcription of specific gene sets upon respective stimuli. We describe that a second Cdk8/19-CycC targeting factor exists, the replication origin firing regulator MTBP that targets the kinase to Med12-independent cellular roles. Both Med12 and MTBP constitute allosteric activators of the enzymatic Cdk8/19-CycC kinase activity in vitro. We describe the structural basis of this activation that involves distinct mechanisms how Med12 and MTBP reposition the T-loop of the kinase independently of T-loop phosphorylation - the canonical mechanism of CDK kinase activation. Our results support the following model: the Cdk8/19-CycC dimer alone has low enzymatic activity, which may help avoid off-target phosphorylation. Med12, MTBP and potentially other as yet unidentified accessory factors, target the kinase to distinct molecular environments, at the same time activating kinase activity for efficient substrate phosphorylation. Our work establishes an unusual mechanism of CDK kinase control and change the current paradigm how Cdk8/19-CycC selects its substrates. Substrate selection of the kinase may be relevant for cancer biology and therapy because Cdk8 is a well-established colorectal cancer promoting factor.

biochemistry↗

A two-gene strategy increases the iron and zinc concentration of wheat flour and improves mineral bioaccesibility for human nutrition.

Dietary deficiencies of iron and zinc cause human malnutrition globally, which can be mitigated by biofortified staple crops. Conventional breeding approaches to increase grain mineral concentrations in wheat (Triticum aestivum L.) have had only limited success so far due to relatively low genetic variation. Here we demonstrate that a transgenic approach combining endosperm-specific expression of the wheat vacuolar iron transporter gene TaVIT2-D with constitutive expression of the rice nicotianamine synthase gene OsNAS2 has the potential to dramatically improve mineral micronutrient intake from wheat products. In two distinct bread wheat cultivars, we show that the VIT-NAS construct led to a two-fold increase in zinc to [~]50 {micro}g g-1 in wholemeal flour and a two-fold increase in both zinc and iron in hand-milled white flour. In highly pure, roller-milled white flour, the concentration of iron was enhanced three-fold to [~]25 {micro}g g-1. A greater than three-fold increase in the level of the natural plant metal chelator nicotianamine in the grain of VIT-NAS lines was associated with improved iron and zinc bioaccessibility in white flour. The growth of VIT-NAS plants in the greenhouse was indistinguishable from untransformed controls. We conclude that the effects of each gene cassette are additive in altering the total concentration and distribution of iron and zinc in wheat grains. This demonstrates the potential of a transgenic approach to enhance the nutritional quality of wheat well beyond what is possible by breeding approaches in order to alleviate dietary mineral deficiencies.

plant biology↗