[Biosynthesis and metabolic engineering of dithiolopyrrolone - A review]

Dithiolopyrrolones are a family of antibiotics that possess the unique pyrrolinonodithiole (4H-[1,2] dithiolo [4, 3-b] pyrrol-5-one) skeleton. This family of natural products can be divided into three subfamilies: N-methyl-N- acylpyrrothine, N-acylpyrrothine and thiomarinols. So far, more than 27 members of this group of natural products have been reported including the well-known antibiotics holomycin, thiolutin, aureothricin and recently isolated thiomarinols. Dithiolopyrrolones exhibit relatively broad-spectrum antibiotic activities against many Gram-positive, Gram-negative bacteria and parasites. Some dithiolopyrrolones even have antitumor activities. In recent years, several dithiolopyrrolone biosynthetic gene clusters have been reported and their biosynthetic mechanisms have also been intensively studied. This review will give an overview about the biosynthesis and metabolic engineering of the dithiolopyrrolone natural products, and provides references to guide the creation of hybrid "unnatural" dithiolopyrrolones with better bioactivity and low toxicity by synthetic biology.