Late biosynthetic genes

PELLETIER, M.K., MURRELL, J., SHIRLEY, B.W., Arabidopsis flavonol synthase and leucoanthocyanidin dioxygenase further evidence for distinct regulation of "early" and "late" flavonoid biosynthetic genes, Plant Physiol., 1997,113, 1437-1445. 

Figure 2.22. Biosynthetic gene clusters for fortimicin (FOR), the putative FOR cluster from Frankia sp. CcI3 (fra cluster, cf. Table 18) and istamycin (1ST) AGAs. D Late cyclitol modification, for all other colors see Figure 2.9. See color plates.

Thus from an analysis of the biosynthetic gene clusters as well as from earlier biosynthetic studies (often with blocked mutants), it is useful to divide the poly-ketide biosynthetic pathway into PKS reactions and post-PKS tailoring steps. Several of the latter were investigated with respect to biosyntheses of angucy-clin(on)es and natural products derived thereof. Intensive studies of various blocked mutant products of Streptomyces fradiae Til 2717 resulted in a well established sequence of the late steps of urdamycin A (281) biosynthesis (Scheme 63) [164]. 

Transcription factors that upregulate strictosidine synthase (132), as well as a transcription factor that coordinately upregu-lates expression of several terpenoid indole alkaloid biosynthetic genes, have been found (133). Several zinc finger proteins that act as transcriptional repressors to tryptophan decarboxylase and strictosidine synthase also have been identified (134). Manipulation of these transcription factors may allow tight control of the regulation of terpenoid indole alkaloid production. Interestingly, expression of a transcription factor from Arabidopsis thaliana in C. roseus cell cultures results in an increase in alkaloid production (135). 

In the late 1990 s, a breakthrough in biosynthesis was reached based on the finding that benzoxazinone and tryptophane biosynthesis have a formal branch point, and indole is a precursor of the benzoxazinones.18 The biosynthetic pathway from indole as the precursor of the benzoxazinone moiety was elucidated both on the levels of the responsible gene cluster discovered and the corresponding enzymes.23 The stepwise oxidation of indole with molecular oxygen by means of... 

Fig. 1. Map of the S. erythraea genome containing genes associated with the late stages of the erythromycin biosynthetic pathway...

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