Abstract: Benzoisochromanequinones antibiotics,a group of bioactive polyketide compounds with aromatic polyketide skeletal cores,are accumulated in streptomycetes. The biosynthesis of benzoisochromanequinones antibiotics has triggered great interest because they not only represent model biosynthetic mechanisms of aromatic polyketide skeletal structures,but also possess a variety of tailoring modifications rendering them highly structural and bioactive diversity. Here we reviewed important advances in biosynthesis of benzoisochromanequinones antibiotics in recent 25 years with focusing on the modification mechanisms of these compounds and on the prospects of the metabolic engineering and pharmaceutical discovery of benzoisochromanequinones antibiotics.