Metabolic engineering of for biosynthesis of -dimethylated anthracyclines.

Daunorubicin and doxorubicin, two anthracycline polyketides produced by , are potent anticancer agents that are widely used in chemotherapy, despite severe side effects. Recent advances have highlighted the potential of producing improved derivatives with reduced side effects by incorporating l-rhodosamine, the -dimethyl analogue of the native amino sugar moiety. In this study, we aimed to produce -dimethylated anthracyclines by engineering the doxorubicin biosynthetic pathway in the industrial strain G001.

Anthracyclines: biosynthesis, engineering and clinical applications.

Covering: January 1995 to June 2021Anthracyclines are glycosylated microbial natural products that harbour potent antiproliferative activities. Doxorubicin has been widely used as an anticancer agent in the clinic for several decades, but its use is restricted due to severe side-effects such as cardiotoxicity. Recent studies into the mode-of-action of anthracyclines have revealed that effective cardiotoxicity-free anthracyclines can be generated by focusing on histone eviction activity, instead of canonical topoisomerase II poisoning leading to double strand breaks in DNA.

Physiological responses of Saccharomyces cerevisiae to industrially relevant conditions: Slow growth, low pH, and high CO levels.

Engineered strains of Saccharomyces cerevisiae are used for industrial production of succinic acid. Optimal process conditions for dicarboxylic-acid yield and recovery include slow growth, low pH, and high CO . To quantify and understand how these process parameters affect yeast physiology, this study investigates individual and combined impacts of low pH (3.