title: Cytochrome c and c1 heme lyases are essential in Plasmodium berghei.
abstract: Malaria parasites possess a de novo heme synthetic pathway. Interestingly, this pathway is dispensable during the blood stages of development in mammalian hosts. The assembly of the two most important hemeproteins, cytochromes c and c1, is mediated by cytochrome heme lyase enzymes. Plasmodium spp. possess two cytochrome heme lyases encoded by separate genes. Given the redundancy of heme synthesis, we sought to determine if heme lyase function also exhibits redundancy. To answer this question, we performed gene knockout experiments. We found that the PBANKA_143950 and PBANKA_0602600 Plasmodium berghei genes encoding cytochrome c (Pbcchl) and cytochrome c1 (Pbcc1hl) heme lyases, respectively, can only be disrupted when a complementary gene is present. In contrast, four genes in the de novo heme synthesis pathway can be disrupted without complementation. This work provides evidence that Pbcchl and Pbcc1hl are both essential and thus may be antimalarial targets.
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors: Navaporn
authors: N
authors: Posayapisit
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors: Warangkhana
authors: W
authors: Songsungthong
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors: Pongpisid
authors: P
authors: Koonyosying
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors: Mofolusho O
authors: MO
authors: Falade
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors: Chairat
authors: C
authors: Uthaipibull
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors: Yongyuth
authors: Y
authors: Yuthavong
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand. Electronic address: philip@biotec.or.th.
authors: Philip J
authors: PJ
authors: Shaw
authors: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Neung, Amphoe Khlong Luang, Pathum Thani 12120, Thailand. Electronic address: sumaleek@biotec.or.th.
authors: Sumalee
authors: S
authors: Kamchonwongpaisan
mesh_terms: D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism*; D003575:Cytochromes c1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D018390:Gene Targeting; D020043:Genes, Essential; D005822:Genetic Vectors / Q000235:genetics; D006418:Heme / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010962:Plasmodium berghei / Q000502:physiology*
chemical_list: D006418:Heme; D045304:Cytochromes c; D003575:Cytochromes c1
keywords: Cytochrome c heme lyase; Gene knockout; Malaria; Pbcc(1)hl; Pbcchl; Plasmodium