Niran Roongsawang

Publications (2)10.47 Total impact

• Article: Biosynthetic studies and genetic engineering of pactamycin analogs with improved selectivity toward malarial parasites.

  Wanli Lu, Niran Roongsawang, Taifo Mahmud
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  ABSTRACT: Pactamycin, one of the most densely functionalized aminocyclitol antibiotics, has pronounced antibacterial, antitumor, antiviral, and antiplasmodial activities, but its development as a clinical drug was hampered by its broad cytotoxicity. Efforts to modulate the biological activity by structural modifications using synthetic organic chemistry have been difficult because of the complexity of its chemical structure. However, through extensive biosynthetic studies and genetic engineering, we were able to produce analogs of pactamycin that show potent antimalarial activity, but lack significant antibacterial activity, and are about 10-30 times less toxic than pactamycin toward mammalian cells. The results suggest that distinct ribosomal binding selectivity or new mechanism(s) of action may be involved in their plasmodial growth inhibition, which may lead to the discovery of new antimalarial drugs and identification of new molecular targets within malarial parasites.
  Chemistry & biology 04/2011; 18(4):425-31. · 6.52 Impact Factor
• Article: Deciphering pactamycin biosynthesis and engineered production of new pactamycin analogues.

  Takuya Ito, Niran Roongsawang, Norifumi Shirasaka, Wanli Lu, Patricia M Flatt, Noer Kasanah, Cristobal Miranda, Taifo Mahmud
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  ABSTRACT: Pactamycin is an aminocyclopentitol-derived natural product that has potent antibacterial and antitumor activities. Sequence analysis of an 86 kb continuous region of the chromosome from Streptomyces pactum ATCC 27456 revealed a gene cluster involved in the biosynthesis of pactamycin. Gene inactivation of the Fe-S radical SAM oxidoreductase (ptmC) and the glycosyltransferase (ptmJ), individually abrogated pactamycin biosynthesis; this confirmed the involvement of the ptm gene cluster in pactamycin biosynthesis. The polyketide synthase gene (ptmQ) was found to support 6-methylsalicylic acid (6-MSA) synthesis in a heterologous host, S. lividans T7. In vivo inactivation of ptmQ in S. pactum impaired pactamycin and pactamycate production but led to production of two new pactamycin analogues, de-6-MSA-pactamycin and de-6-MSA-pactamycate. The new compounds showed equivalent cytotoxic and antibacterial activities with the corresponding parent molecules and shed more light on the structure-activity relationship of pactamycin.
  ChemBioChem 09/2009; 10(13):2253-65. · 3.94 Impact Factor