Post-Translational Tyrosine Geranylation in Cyanobactin Biosynthesis

Maho Morita, Yue Hao, Jouni K. Jokela, Debosmita Sardar, Zhenjian Lin, Kaarina Sivonen, Satish K. Nair, Eric W. Schmidt

Research output: Contribution to journalArticlepeer-review


Prenylation is a widespread modification that improves the biological activities of secondary metabolites. This reaction also represents a key modification step in biosyntheses of cyanobactins, a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) produced by cyanobacteria. In cyanobactins, amino acids are commonly isoprenylated by ABBA prenyltransferases that use C5 donors. Notably, mass spectral analysis of piricyclamides from a fresh-water cyanobacterium suggested that they may instead have a C10 geranyl group. Here we characterize a novel geranyltransferase involved in piricyclamide biosynthesis. Using the purified enzyme, we show that the enzyme PirF catalyzes Tyr O-geranylation, which is an unprecedented post-translational modification. In addition, the combination of enzymology and analytical chemistry revealed the structure of the final natural product, piricyclamide 7005E1, and the regioselectivity of PirF, which has potential as a synthetic biological tool providing drug-like properties to diverse small molecules.

Original languageEnglish (US)
Pages (from-to)6044-6048
Number of pages5
JournalJournal of the American Chemical Society
Issue number19
StatePublished - May 16 2018

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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