Production, Trade, Prices, Exchange Rates and Equilibration in Large Experimental Economies

We study market equilibration in laboratory economies that are larger and more complex than any that have been studied experimentally to date. Complexity is derived from the fact that the economies are international in economic structure with multiple input, output, and foreign exchange markets in operation. The economies have twenty-one markets and due to the fact that they have roughly �fifty agents, the economies are characterized by several hundred equations. In spite of the complexity and interdependence of the economy, the results demonstrate the substantial power of the general equilibrium model of perfect competition to predict the direction of movement of market-level variables. Empirical patterns in the convergence process are explored and described

An Experimental Investigation of the Patterns of International Trade

This study is the first attempt to create and study a laboratory economy with some of the prominent features of an international economic system. The concept of multiple "countries" in which each country has its own technology, preferences and resource endowments, is introduced and operationalized. The questions posed in the study are related to the law of comparative advantage, factor price equalization, terms of trade, efficiency in production and exchange as guided by multiple and interacting markets and the effects of tariffs on international transactions. The study builds on previous work in the experimental study of general equilibrium phenomena

An Experimental Investigation of the Patterns of International Trade

This study is the first attempt to create and study a laboratory economy with some of the prominent features of an international economic system. The concept of multiple "countries" in which each country has its own technology, preferences and resource endowments, is introduced and operationalized. The questions posed in the study are related to the law of comparative advantage, factor price equalization, terms of trade, efficiency in production and exchange as guided by multiple and interacting markets and the effects of tariffs on international transactions. The study builds on previous work in the experimental study of general equilibrium phenomena

Streamlining bioactive molecular discovery through integration and automation

The discovery of bioactive small molecules is generally driven via iterative design–make–purify–test cycles. Automation is routinely harnessed at individual stages of these cycles to increase the productivity of drug discovery. Here, we describe recent progress to automate and integrate two or more adjacent stages within discovery workflows. Examples of such technologies include microfluidics, liquid-handling robotics and affinity-selection mass spectrometry. The value of integrated technologies is illustrated in the context of specific case studies in which modulators of targets, such as protein kinases, nuclear hormone receptors and protein–protein interactions, were discovered. We note that to maximize impact on the productivity of discovery, each of the integrated stages would need to have both high and matched throughput. We also consider the longer-term goal of realizing the fully autonomous discovery of bioactive small molecules through the integration and automation of all stages of discovery

Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit

Metabolic engineering of microorganisms to produce desirable products on an industrial scale can result in unbalanced cellular metabolic networks that reduce productivity and yield. Metabolic fluxes can be rebalanced using dynamic pathway regulation, but few broadly applicable tools are available to achieve this. We present a pathway-independent genetic control module that can be used to dynamically regulate the expression of target genes. We apply our module to identify the optimal point to redirect glycolytic flux into heterologous engineered pathways in Escherichia coli, resulting in titers of myo-inositol increased 5.5-fold and titers of glucaric acid increased from unmeasurable to >0.8 g/L, compared to the parent strains lacking dynamic flux control. Scaled-up production of these strains in benchtop bioreactors resulted in almost ten-and fivefold increases in specific titers of myo-inositol and glucaric acid, respectively. We also used our module to control flux into aromatic amino acid biosynthesis to increase titers of shikimate in E. coli from unmeasurable to >100 mg/L. ©2017 Nature America, Inc., part of Springer Nature.NSF CAREER program (Grant No. CBET-0954986)Synthetic Biology Engineering Research Center - SynBERC (Grant No. EEC-0540879)Division of Molecular and Cellular Biosciences (Grant No. MCB-1517913)Biotechnology Training Program of the NIH (Grant No. T32GM008334)USDA National Institute of Food and Agriculture Postdoc Fellowship (Grant No. 2013-67012-21022

Improvement of glucaric acid production in E. coli via dynamic control of metabolic fluxes

D-glucaric acid can be used as a building block for biopolymers as well as in the formulation of detergents and corrosion inhibitors. A biosynthetic route for production in Escherichia coli has been developed (Moon et al., 2009), but previous work with the glucaric acid pathway has indicated that competition with endogenous metabolism may limit carbon flux into the pathway. Our group has recently developed an E. coli strain where phosphofructokinase (Pfk) activity can be dynamically controlled and demonstrated its use for improving yields and titers of the glucaric acid precursor myo-inositol on glucose minimal medium. In this work, we have explored the further applicability of this strain for glucaric acid production in a supplemented medium more relevant for scale-up studies, both under batch conditions and with glucose feeding via in situ enzymatic starch hydrolysis. It was found that glucaric acid titers could be improved by up to 42% with appropriately timed knockdown of Pfk activity during glucose feeding. The glucose feeding protocol could also be used for reduction of acetate production in the wild type and modified E. coli strains. Keywords: Dynamic metabolic engineering, Glucaric acid, Protein degradation, Synthetic biolog