Browsing by Author "Deng, Z."
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Item Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps(Chemistry & Biology, 2015-12) Huang, S.; Elsayed, S.S.; Lv, M.; Tabudravu, J.; Rateb, E.M.; Gyampoh, R.; Kyeremeh, K.; Ebel, R.; Jaspars, M.; Deng, Z.; Yu, YI.; Deng, H.Neocarazostatin A (NZS) is a bacterial alkaloid with promising bioactivities against free radicals, featuring a tricyclic carbazole nucleus with a prenyl moiety at C-6 of the carbazole ring. Here, we report the discovery and characterization of the biosynthetic pathway of NZS through genome mining and gene inactivation. The in vitro assays characterized two enzymes: NzsA is a P450 hydroxylase and NzsG is a new phytoene-synthase-like prenyltransferase (PTase). This is the first reported native PTase that specifically acts on the carbazole nucleus. Finally, our in vitro reconstituted experiment demonstrated a coupled reaction catalyzed by NzsG and NzsA tailoring the NZS biosynthesis.Item Enzymatic Reconstitution and Biosynthetic Investigation of the Bacterial Carbazole Neocarazostatin A(The Journal of Organic Chemistry, 2019-11-15) Kyeremeh, K.; Liu, Y.; Su, L.; Fang, Q.; Tabudravu, J.; Yang, X.; Rickaby, K.; Trembleau, L.; Deng, Z.; Deng, H.; Yu, Y.Tricyclic carbazole is an important scaffold in many naturally occurring metabolites, as well as valuable building blocks. Here we report the reconstitution of the ring A formation of the bacterial neocarazostatin A carbazole metabolite. We provide evidence of the involvement of two unusual aromatic polyketide proteins. This finding suggests how new enzymatic activities can be recruited to specific pathways to expand biosynthetic capacities. Finally, we leveraged our bioinformatics survey to identify the untapped capacity of carbazole biosynthesisItem A ThDP-dependent enzymatic carboligation reaction involved in Neocarazostatin A tricyclic carbazole formation(2016) Su, L.; Lv, M.; Kyeremeh, K.; Deng, Z.; Deng, H.; Yu, Y.Although the biosynthetic pathway of Neocarazostatin A (1) has been identified, the detailed enzymatic reactions underlying the assembly of the carbazole ring still remain largely unknown. We demonstrate here that NzsH, a putative thiamine diphosphate dependent enzyme, can catalyze an acyloin coupling reaction between indole-3-pyruvate and pyruvate to generate a β-ketoacid intermediate. Our findings thus shed light on further characterization of the unusual biosynthetic pathway of the bacterial tricyclic carbazole alkaloids. © The Royal Society of Chemistry 2016.