A microbial supply chain for production of the anti-cancer drug vinblastine

International audienceAbstract Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine 1 . As MIAs are difficult to chemically synthesize, the world’s supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant Catharanthus roseus , which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale 2,3 . Here, we demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. The study showcases a very long biosynthetic pathway refactored into a microbial cell factory, including 30 enzymatic steps beyond the yeast native metabolites geranyl pyrophosphate and tryptophan to catharanthine and vindoline. In total, 56 genetic edits were performed, including expression of 34 heterologous genes from plants, as well as deletions, knock-downs and overexpression of ten yeast genes to improve precursor supplies towards de novo production of catharanthine and vindoline, from which semisynthesis to vinblastine occurs. As the vinblastine pathway is one of the longest MIA biosynthetic pathways, this study positions yeast as a scalable platform to produce more than 3,000 natural MIAs and a virtually infinite number of new-to-nature analogues

Comparing inequalities in the labour market from a segmentation perspective

Production of INCASI Project H2020-MSCA-RISE-2015 GA 691004The purpose of this chapter is to carry out a comparative analysis of labour markets in Europe and Latin America from the perspective of segmentation in order to explain the processes of social inequality that arise in the workplace, in light of recent trends in global socio-economic changes. The chapter proposes two main objectives. The first is to perform a comparative descriptive analysis of the main features of labour markets among 60 European and Latin American countries. The second objective is to propose a model of comparative analysis of labour inequality from the theoretical perspective of the segmentation of the labour market and structural heterogeneity. We will focus our analysis by selecting two countries, Spain and Argentina, which both underwent a late development of capitalism. The following general hypothesis is formulated: Spain and Argentina, having clearly differentiated features in economic structure, level of development, institutional frameworks and socio-historical processes, show common dynamics in the structuring of the capitalist labour market between a primary and secondary segment. Using equivalent databases on the workforce a typology of segmentation of employment is constructed that show, in addition to the specificities of each country, the similarities in the structuring of the labour market

Social times, reproduction and social inequality at work : contrasts and comparative perspectives between countries

Production of INCASI Project H2020-MSCA-RISE-2015 GA 691004If the focus is placed specifically on the problem of work and family, the daily life of people and their use of time are a main problem. This time is expressed in both freely available time, which is related to activities, and time of the productive and reproductive sphere. This chapter considers work in a broad sense and takes into account the sexual division of labour. Specifically, this chapter will explore transformations in time use and social inequality in unpaid work. For this purpose, a comparative analysis of time-use surveys will be used, analysing the time spent, and the time dedicated to household chores in Chile, Argentina, Uruguay and Spain. From an analytical viewpoint, the analysis will place social reproduction at the centre of the socio-economic system, showing that the economic crisis has affected women and men differently, and that in both Europe and Latin America the family pattern is being replaced by a dominant family model of a male provider and a double presence of women. The large-scale incorporation of women into the labour market has emphasised the role that women assume in the domestic sphere perpetuating gender segregation in employment and in domestic and care work