Enzymatic amide bond formation: synthesis of aminooxo-acids through a Mycobacterium smegmatis acyltransferase

A highly-productive strategy based on the use of an acyltransferase from Mycobacterium smegmatis (MsAcT), for the preparation of aminooxo-acids in water was developed. 1 M-scale biotransformations were carried out with excellent yields (68-94%) and rapid reactions (0.5-5 h) starting from anilines and a range of different anhydrides. The high substrate-to-catalyst ratio (M-substrate/M-catalyst: 25 000), enzymatic stability (one month without any activity loss), and excellent protein purification yields (130 mg from 2 g of wet cell paste) made this process a green and cost-efficient approach, which was successfully applied for the preparation of a key intermediate of SAHA synthesis.

Automated summary

A highly-productive strategy using an acyltransferase from Mycobacterium smegmatis was developed for the preparation of aminooxo-acids in water. The reaction showed excellent yields and rapid reactions, and the process was considered to be cost-effective and environmentally friendly. The method was successfully applied for the preparation of a key intermediate in SAHA synthesis.