The reaction mechanisms of the pyridoxal phosphate (PLP)-dependent enzymes LmbF and CcbF—involved in the biosynthesis of the antibiotic lincosamide—are characterized here. Structure–function analyses reveal structural features responsible for S-alkyl moiety diversification in lincosamides. Using structure- and calculation-based enzyme engineering, the selectivity profiles of these enzymes are designed to generate an unnatural lincosamide derivative.
- Takahiro Mori
- Yoshitaka Moriwaki
- Ikuro Abe