SynBioFromLeukipposInstitute

by
Chiarabelli, Cristiano; Luisi, Pier Luigi

"Although both the most popular form of synthetic biology (SB) and chemical synthetic biology (CSB) share the biotechnologically useful aim of making new forms of life, SB does so by using genetic manipulation of extant microorganism, while CSB utilises classic chemical procedures in order to obtain biological structures which are non-existent in nature. The main query concerning CSB is the philosophical question: why did nature do this, and not that? The idea then is to synthesise alternative structures in order to understand why nature operated in such a particular way. We briefly present here some various examples of CSB, including those cases of nucleic acids synthesised with pyranose instead of ribose, and proteins with a reduced alphabet of amino acids; also we report the developing research on the “never born proteins” (NBP) and “never born RNA” (NBRNA), up to the minimal cell project, where the issue is the preparation of semi-synthetic cells that can perform the basic functions of biological cells."

 http://bit.ly/1crgtqj

by
Patrick M. Shi1, Jan Zarzycki, Krishna K. Niyogi and Cheryl A. Kerfeld

"Global photosynthetic productivity is limited by the enzymatic assimilation of CO2 into organic carbon compounds. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the carboxylating enzyme of the Calvin-Benson (CB) cycle, poorly discriminates between CO2 and O2, leading to photorespiration and the loss of fixed carbon and nitrogen. With the advent of synthetic biology, it is now feasible to design, synthesize and introduce biochemical pathways in vivo. We engineered a synthetic photorespiratory bypass based on the 3-hydroxypropionate bi-cycle into the model cyanobacterium, Synechococcus elongatus sp. PCC 7942. The heterologously expressed cycle is designed to function as both a photorespiratory bypass and an additional CO2-fixing pathway, supplementing the CB cycle. We demonstrate the function of all six introduced enzymes and identify bottlenecks to be targeted in subsequent bioengineering. These results have implications for efforts to improve photosynthesis, and for the "green" production of high-value products of biotechnological interest."

 http://bit.ly/1kvbwPS

by
Chiang AW, Hwang MJ.

"An increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing. Here, we addressed this problem by developing a computational pipeline to mathematically simulate a gene circuit for a comprehensive range and combination of the kinetic parameters of the biological components that constitute the gene circuit.

 http://bit.ly/1frVPa2

by
Depaoli HC, Borland AM, Tuskan GA, Cushman JC, Yang X.

"To meet future food and energy security needs, which are amplified by increasing population growth and reduced natural resource availability, metabolic engineering efforts have moved from manipulating single genes/proteins to introducing multiple genes and novel pathways to improve photosynthetic efficiency in a more comprehensive manner. Biochemical carbon-concentrating mechanisms such as crassulacean acid metabolism (CAM), which improves photosynthetic, water-use, and possibly nutrient-use efficiency, represent a strategic target for synthetic biology to engineer more productive C3 crops for a warmer and drier world. One key challenge for introducing multigene traits like CAM onto a background of C3 photosynthesis is to gain a better understanding of the dynamic spatial and temporal regulatory events that underpin photosynthetic metabolism. With the aid of systems and computational biology, vast amounts of experimental data encompassing transcriptomics, proteomics, and metabolomics can be related in a network to create dynamic models. Such models can undergo simulations to discover key regulatory elements in metabolism and suggest strategic substitution or augmentation by synthetic components to improve photosynthetic performance and water-use efficiency in C3 crops. Another key challenge in the application of synthetic biology to photosynthesis research is to develop efficient systems for multigene assembly and stacking. Here, we review recent progress in computational modelling as applied to plant photosynthesis, with attention to the requirements for CAM, and recent advances in synthetic biology tool development. Lastly, we discuss possible options for multigene pathway construction in plants with an emphasis on CAM-into-C3 engineering."
http://bit.ly/1o6oPUg

A great review by Yamanaka et al

http://bit.ly/1ndpIM4

by
Ana Lúcia Leitãoa,  Francisco J. Enguita

"Secondary metabolic pathways of fungal origin provide an almost unlimited resource of new compounds for medical applications, which can fulfill some of the, currently unmet, needs for therapeutic alternatives for the treatment of a number of diseases. Secondary metabolites secreted to the extracellular medium (extrolites) belong to diverse chemical and structural families, but the majority of them are synthesized by the condensation of a limited number of precursor building blocks including amino acids, sugars, lipids and low molecular weight compounds also employed in anabolic processes. In fungi, genes related to secondary metabolic pathways are frequently clustered together and show a modular organization within fungal genomes. The majority of fungal gene clusters responsible for the biosynthesis of secondary metabolites contain genes encoding a high molecular weight condensing enzyme which is responsible for the assembly of the precursor units of the metabolite. They also contain other auxiliary genes which encode enzymes involved in subsequent chemical modification of the metabolite core. Synthetic biology is a branch of molecular biology whose main objective is the manipulation of cellular components and processes in order to perform logically connected metabolic functions. In synthetic biology applications, biosynthetic modules from secondary metabolic processes can be rationally engineered and combined to produce either new compounds, or to improve the activities and/or the bioavailability of the already known ones. Recently, advanced genome editing techniques based on guided DNA endonucleases have shown potential for the manipulation of eukaryotic and bacterial genomes. This review discusses the potential application of genetic engineering and genome editing tools in the rational design of fungal secondary metabolite pathways by taking advantage of the increasing availability of genomic and biochemical data."


http://bit.ly/NsbMRQ

by
Sarpeshkar R.

"We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations."

http://1.usa.gov/1dA9Lcp