Structural highlights
Function
[PIKA1_STRVZ] Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone) (PubMed:18512859, PubMed:19437523). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide.[1] [2] [3] [4]
References
- ↑ Tang L, Fu H, Betlach MC, McDaniel R. Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthase. Chem Biol. 1999 Aug;6(8):553-8. doi: 10.1016/S1074-5521(99)80087-8. PMID:10421766 doi:https://dx.doi.org/10.1016/S1074-5521(99)80087-8
- ↑ Gupta S, Lakshmanan V, Kim BS, Fecik R, Reynolds KA. Generation of novel pikromycin antibiotic products through mutasynthesis. Chembiochem. 2008 Jul 2;9(10):1609-16. doi: 10.1002/cbic.200700635. PMID:18512859 doi:https://dx.doi.org/10.1002/cbic.200700635
- ↑ Yan J, Gupta S, Sherman DH, Reynolds KA. Functional dissection of a multimodular polypeptide of the pikromycin polyketide synthase into monomodules by using a matched pair of heterologous docking domains. Chembiochem. 2009 Jun 15;10(9):1537-43. doi: 10.1002/cbic.200900098. PMID:19437523 doi:https://dx.doi.org/10.1002/cbic.200900098
- ↑ Kittendorf JD, Sherman DH. The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis. Bioorg Med Chem. 2009 Mar 15;17(6):2137-46. doi: 10.1016/j.bmc.2008.10.082. Epub , 2008 Nov 5. PMID:19027305 doi:https://dx.doi.org/10.1016/j.bmc.2008.10.082
