Frederick F Twigg1, Wenlong Cai1, Wei Huang1, Joyce Liu2, Michio Sato1, Tynan J Perez3, Jiaxin Geng4, Moriel J Dror1, Ismael Montanez3, Tate L Tong1, Hyunsu Lee3, Wenjun Zhang1,5. 1. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, 2151 Berkeley Way, Berkeley, CA, 94704, USA. 2. Department of Bioengineering, University of California, Berkeley, 2151 Berkeley Way, Berkeley, CA, 94704, USA. 3. Department of Chemistry, University of California, Berkeley, 2151 Berkeley Way, Berkeley, CA, 94704, USA. 4. Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, 94704, USA. 5. Chan Zuckerberg Biohub, 499 Illinois St., San Francisco, CA, 94158, USA.
Abstract
Triacsins are a family of natural products having in common an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, their biosynthesis has remained unknown. Here we report the identification of the triacsin biosynthetic gene cluster in Streptomyces aureofaciens ATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producer Streptomyces tsukubaensis NRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performed in vivo to advance the understanding of N-hydroxytriazene biosynthesis.
Triacsins are a family of natural products having in common ann class="Chemical">N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, their biosynthesis has remained unknown. Here we report the identification of the triacsin biosynthetic gene cluster in Streptomyces aureofaciens ATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producer Streptomyces tsukubaensis NRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performed in vivo to advance the understanding of N-hydroxytriazene biosynthesis.
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