Ahmad Abdullah Mannan

Imperial College London | Imperial · Department of Bioengineering

Metabolite biosensors are central to current efforts towards precision engineering of metabolism. Although most research has focused on building new biosensors, their tunability remains poorly understood and is a fundamental aspect for their broad applicability. Here we asked how genetic modifications shape the dose- response curve of biosensors ba...

Bacteria can be harnessed to synthesise high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, use of expensive chemical inducers limits scalability of this approach for biotechnolog...

Motivation A widely applicable strategy to create cell factories is to knock out (KO) genes or reactions to redirect cell metabolism so that chemical synthesis is made obligatory when the cell grows at its maximum rate. Synthesis is thus growth-coupled, and the stronger the coupling the more deleterious any impediments in synthesis are to cell grow...

Bacteria can be engineered to manufacture chemicals, but it is unclear how to optimally engineer a single cell to maximise production performance from batch cultures. Moreover, the performance of engineered production pathways is affected by competition for the host’s native resources. Here, using a “host-aware” computational framework which captur...

Staphylococcus aureus (SA) colonizes and can damage skin in atopic dermatitis lesions, despite being commonly found with Staphylococcus epidermidis (SE), a commensal that can inhibit SA’s virulence and kill SA. In this study, we developed an in silico model, termed a virtual skin site, describing the dynamic interplay between SA, SE, and the skin b...

Motivation - Genome-scale models are used to predict KOs that will reroute cell metabolism for chemical overproduction. A promising strategy to create cell factories with robust chemical synthesis is do KOs that make synthesis obligatory at high growth, i.e. growth-coupling. This enable us to evolve and select KO mutants on growth and attain evolut...

Motivation: A widely applicable strategy for developing evolutionarily robust cell factories is to knock out (KO) genes or reactions to couple chemical synthesis with cell growth. Genome-scale metabolic models enable their rational design, but KOs that provide growth-coupling (gc) are rare in the immense design space, making searching difficult and...

Recent progress in synthetic biology allows the construction of dynamic control circuits for metabolic engineering. This technology promises to overcome many challenges encountered in traditional pathway engineering, thanks to their ability to self-regulate gene expression in response to bioreactor perturbations. The central components in these con...

Poster of our published theoretical work on how to engineer a genetic circuit for use as a dynamic control switch that irreversibly switches the metabolism of microbes from growth to the synthesis of a chemical product of interest, upon temporary induction with a cheap natural nutrient such as oleic acid.

Bacteria can be harnessed for the synthesis of high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, chemical induction via IPTG and other gratuitous inducers is extremely expensive...

Microbes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required for survival under the new nutritional conditions. Yet, lit...

Problem: Inducible control can switch cell metabolism from growth to chemical production, overcoming their inherent trade-off, but, need for constant induction by expensive inducers makes industrial-scale production infeasible. Question: Can we re-wire an endogenous uptake system to engineer a switch that needs only temp. stimulus with a cheap nut...

Metabolic engineering has enabled the production of a wealth of chemicals with microorganisms. Classic strategies for pathway engineering rely on the expression of heterologous enzymes in a host that convert native intermediates into target products. Although traditional implementations are based on open-loop control, recent advances in gene circui...

Microbes adapt their metabolism to take advantage of nutrients in their environment. Upon changes in nutrient conditions, transcriptional programs adapt pathway expression to meet the cellular energy budget. Since nutrient abundance may change frequently, rapid pathway recovery is just as important as fast activation. Yet little is known about the...

Metabolic engineering has enabled the production of a wealth of chemicals with microorganisms. Classic strategies for pathway engineering rely on the expression of heterologous enzymes in a host that convert native intermediates into target products. Although traditional implementations are based on open-loop control, recent advances in gene circui...

Advances in metabolic engineering have led to the synthesis of a wide variety of valuable chemicals in microorganisms. The key to commercializing these processes is the improvement of titer, productivity, yield, and robustness. Traditional approaches to enhancing production use the “push–pull-block” strategy that modulates enzyme expression under s...

Poster summarizing our study elucidating the principles of designing and engineering transcription factor-based biosensors, for applications in metabolic engineering and synthetic biology.

How do cells transmit biochemical signals accurately? It turns out, pushing and pulling can go a long way.

Systems Biology has established numerous approaches for mechanistic modelling of molecular networks in the cell and a legacy of models. The current frontier is the integration of models expressed in different formalisms to address the multi-scale biological system organisation challenge. We present MUFINS software, implementing a unique set of appr...

An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, lim...

Microarray data and analysis for known mutants, assessment of bias in data and ROC analysis. An Excel file containing TraSH data for mixes of known mutants, an assessment of bias within the TraSH data and receiver operating characteristic (ROC) analysis.

Flux variable analysis. An Excel file containing maximal and minimal reaction fluxes compatible with maximal flux to biomass were computed for minimal media agar and serum.

Neisseria meningitidis is an important human commensal and pathogen that causes several thousand deaths each year, mostly in young children. How the pathogen replicates and causes disease in the host is largely unknown, particularly the role of metabolism in colonization and disease. Completed genome sequences are available for several strains but...

Computational procedure for the simulation of fitting experimental data.

Effects of initial metabolite concentrations on the fermentation characteristics.

Table S1 - Ruled used for the simulation.

Simulation result of wild type and Ppc mutant in batch culture.

Simulation result of wild type and Ppc mutant in continuous culture.

Simulation result of wild type and Pck mutant in continuous culture.

Simulation result of wild type and Pyk mutant in batch culture.

Simulation result of wild type and Pyk mutant in continuous culture.

It is quite important to simulate the metabolic changes of a cell in response to the change in culture environment and/or specific gene knockouts particularly for the purpose of application in industry. If this could be done, the cell design can be made without conducting exhaustive experiments, and one can screen out the promising candidates, proc...