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A Type I/Type III PKS Hybrid Generates Cinnamomycin A-D

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卷 25, 期 15, 页码 2560-2564

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AMER CHEMICAL SOC
DOI: 10.1021/acs.orglett.3c002932560Org

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By genome mining, we have discovered a new type I/type III PKS hybrid called cinnamomycin A-D, which is derived from 3,5-dihydroxybenzoic acid. Through genetic manipulation, enzymatic reaction, and precursor feeding, we proposed the biosynthetic pathway of cinnamomycins.
3,5-Dihydroxybenzoic acid (3,5-DHBA), biosynthesized by type III PKS and tailoring enzymes, is an unconventional starter unit for bacterial type I PKS. Genome mining of 3,5-DHBA-specific biosynthetic gene clusters could lead to discovering new type I/type III PKS hybrids. Herein, we report the discovery and characterization of atypical compounds, namely cinnamomycin A-D, exhibiting selective antiproliferative activity. The biosynthetic pathway of cinnamomycins was proposed based on genetic manipulation, enzymatic reaction, and precursor feeding.

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