Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches

Intercultural Education for Intercultural Competence: A New Kind of Literacy for Sustainable Development

The concept of culture is subject to many different interpretations. For the present purpose, the wide-ranging definition of Pederson (2000), as summarized by Corey et al. (2011), would appear suitable. In this definition culture was conceptualized as including “demographic variables such as age, gender, and place of residence; status variables such as social, educational and economic background; formal and informal affiliations; and the ethnographic variables of nationality, ethnicity, language, and religion” (p.115) ..