Leinamycin, biosynthesis

Tang GL, Cheng YQ, Shen B. Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase. Chem. Biol. 2004 11 33-45. 

Most of the latest publications on NRPS substrate specificity are focused on A domain specificity because their substrate screening is straightforward in terms of biosynthetic substrate form (free amino acids/fatty acids/aryl acids) and T domain substrates (one T domain). Four studies focus on substrate specificity of NRPS loading modules of microcystin biosynthesis,97 mycosubtilin biosynthesis,51 daptomycin biosynthesis,108 and leinamycin biosynthesis.108 The A domains of microcystin, mycosubtilin, and daptomycin biosynthesis initiation showed fatty acid specificity. The initial domain from leinamycin biosynthesis has D-amino acid specificity. Another paper presents the elucidation of aryl acid-specific AsbC adenylation enzyme from petrobactin biosynthesis.104... 

Figure 17 The loading module of leinamycin biosynthesis, (a) Loading module components (LnmQ and LnmP) of leinamycin synthetase and leinamycin structure, (b) Substrate screening assays of LnmQ. D-Alanine and glycine loading was detected by ESI-MS (observed and calculated mass shifts of holo LnmP).

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