Sequential Allylic Alcohol Formation by a Multifunctional Cytochrome P450 Monooxygenase with Rare Redox Partners.
Hak Joong KimKeishi IshidaMie Ishida-ItoChristian HertweckPublished in: Angewandte Chemie (International ed. in English) (2022)
Caryoynencin is a toxic and antifungal fatty acid derivative produced by a number of plant-pathogenic and insect-protective bacteria (Trinickia caryophylli and Burkholderia spp.). In addition to the reactive tetrayne unit, the presence of an allylic alcohol moiety is critical for antimicrobial activities. By a combination of mutational analyses, heterologous expression and in vitro reconstitution experiments we show that the cytochrome P450 monooxygenase CayG catalyzes the complex transformation of a saturated carbon backbone into an allylic alcohol. Unexpectedly, CayG employs a ferritin-like protein (CayK) or a rubredoxin (CayL) component for electron transport. A desaturation-hydroxylation sequence was deduced from a time-course study and in vitro biotransformations with pathway intermediates, substrate analogues, protegencin congeners from Pseudomonas protegens Pf-5, and synthetic derivatives. This unusual multifunctional oxygenase may inspire future biocatalytic applications.
Keyphrases
- drug delivery
- alcohol consumption
- fatty acid
- poor prognosis
- cancer therapy
- staphylococcus aureus
- candida albicans
- escherichia coli
- amino acid
- current status
- metal organic framework
- electron transfer
- saccharomyces cerevisiae
- hiv testing
- plant growth
- molecular dynamics simulations
- antiretroviral therapy
- hiv infected
- genetic diversity