Naturally occurring lactams, such as the polyketide-derived macrolactams, provide a diverse class of natural products that could enhance existing chemically produced lactams. Although β-amino acid loading in the fluvirucin B2 polyketide pathway was proposed by a previously identified putative biosynthetic gene cluster, biochemical characterization of the complete loading enzymes has not been described. Here we elucidate the complete biosynthetic pathway of the β-amino acid loading pathway in fluvirucin B2 biosynthesis. We demonstrate the promiscuity of the loading pathway to utilize a range of amino acids and further illustrate the ability to introduce non-native acyl transferases to selectively transfer β-amino acids onto a polyketide synthase (PKS) loading platform. The results presented here provide a detailed biochemical description of β-amino acid selection and will further aid in future efforts to develop engineered lactam-producing PKS platforms.
Barajas, J. F., Zargar, A., Pang, B., Benites, V. T., Gin, J., Baidoo, E. E. K., ... Keasling, J. D. (2018). Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B2 Biosynthesis. Chembiochem, 19(13), 1391-1395. https://doi.org/10.1002/cbic.201800169