The chondramides are mixed non-ribosomal peptide/polyketide secondary metabolites produced by the myxobacterium Chondromyces crocatus Cm c5, which exhibit strong cytotoxic activity. On the basis of their striking structural similarity to the marine depsipeptides jaspamides, the chondramides have been assumed to incorporate a (R)-beta-tyrosine moiety, an expectation we confirm here. Thus, the recent sequencing of the chondramide biosynthetic gene cluster provided the opportunity to probe the shared origin of this unusual beta-amino acid. We demonstrate here that (R)-beta-tyrosine is produced directly from l-tyrosine by the aminomutase CmdF. Along with the tyrosine aminomutase SgcC4 from the C-1027 enediyne pathway, this enzyme belongs to a novel family of tyrosine aminomutases related to the ammonium lyase family of enzymes but exhibits opposite facial selectivity for the hydroxycinnamate intermediate. We also show that the adenylation (A) domain in the chondramide pathway, which activates the beta-tyrosine building block, exhibits the required preference for (R)-beta-tyrosine, further arguing against alternative origins for the moiety in the chondramides. Comparison to the (S)-beta-tyrosine specific A domain SgcC1 should enhance our understanding of the structural and stereochemical determinants guiding amino acid selection by non-ribosomal peptide synthetase multienzymes.