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Gene Review

OXSM  -  3-oxoacyl-ACP synthase, mitochondrial

Homo sapiens

Synonyms: Beta-ketoacyl-ACP synthase, FASN2D, FLJ20604, KASI, KS
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Disease relevance of OXSM

  • Similarly, a human FAS cDNA encoding domain I (beta-ketoacyl synthase, acetyl-CoA and malonyl-CoA transacylases, and beta-hydroxyacyl dehydratase) was cloned and expressed in E. coli using pMAL-c2 [1].
  • Here we characterize the kinetic class of a group of 16 Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies [2].
  • Phylogenetic analysis of the ketosynthase (KS) gene sequences of marine sponge-derived Salinispora strains of actinobacteria indicated that the polyketide synthase (PKS) gene sequence most closely related to that of Salinispora was the rifamycin B synthase of Amycolatopsis mediterranei [3].
  • Regional distribution but not severity of cerebellar volume deficits is similar in alcoholic individuals whether or not complicated by KS and relates to ataxia [4].
  • For their deduced amino acid sequences, eight were identical to three known KSs from Sorangium and Magnetospirillum, while the others showed 54-83% identities to the modular KS domains reported from various microorganisms [5].

High impact information on OXSM

  • The crystal structure also reveals that the active site residue Cys-199 of the KS domain is separated from the active site residue Ser-642 of the AT domain by approximately 80 Angstrom [6].
  • In this study, we describe the de novo synthesis of C75 based on the known mechanism of action of cerulenin and the theoretical reaction intermediates of the beta-ketoacyl synthase moiety of FAS [7].
  • All the partial activities of human FAS are comparable to those of other animal FASs, except for the beta-ketoacyl synthase, whose significantly lower activity is attributable to the low 4'-phosphopantetheine content of HepG2 FAS [8].
  • The phylogenetic distribution of acyltransferase and KS domain sequences revealed that multiple gene duplications, gene losses, as well as horizontal gene transfer (HGT) have contributed to the evolution of PKS I in bacteria [9].
  • Our study shows that several KSHV-encoded homologues of cellular cytokines, chemokines, and antiapoptotic factors are expressed during the viral lytic cycle in PEL cell lines and in KS biopsies [2].

Chemical compound and disease context of OXSM


Biological context of OXSM

  • The initial steps leading to the formation of GA result from the two-step cyclization of geranylgeranyl diphosphate (GGDP) to (-)-kaurene via the action of two terpene cyclases (-)-copalyl diphosphate synthase (CPS) and (-)-kaurene synthase (KS) [11].
  • The KS gene has been duplicated in the S. rebaudiana genome and both the KS and CPS genes are highly expressed in mature leaves, a pattern opposite to that found with GA biosynthesis [11].
  • Using DEBS 1-TE, a bimodular derivative of DEBS, we aimed to determine whether the beta-ketosynthase (KS) domain responsible for condensation in the first module also has the ability to prime its own biosynthesis by catalyzing the decarboxylation of methylmalonyl-CoA to produce propionyl-CoA [12].
  • The KS domain phylogeny of 23 PKSI clusters was determined [13].
  • The catalytic mechanism of the beta-ketoacyl synthase domain of the multifunctional fatty acid synthase has been investigated by a combination of mutagenesis, active-site titration, product analysis, and product inhibition [14].

Anatomical context of OXSM

  • The KS lesions in HIV-positive patients tended to have dissecting blood vessels (14/33 cases; 42%) unlike those seen in HIV-negative patients (0/14 cases; 0%) (p=0.004) [15].
  • On the basis of these findings we suggest that the assessment of KS peptide by ELISIAs may provide a useful means of monitoring proteoglycan breakdown products in biological fluids (e.g. synovial fluids or blood) and for evaluating the effects that antiarthritic drugs may have on this process [16].
  • The ELISIA technique was capable of quantitating the keratan sulphate peptides (KS peptides) in fluids within the range of 100-2,000 ng/ml by using the monoclonal antibody line 1/20/5-D-4 and human articular cartilage KS peptides as standard reagents [16].

Associations of OXSM with chemical compounds


Analytical, diagnostic and therapeutic context of OXSM

  • In situ hybridization of KS biopsies showed that about 3% of spindle-shaped tumor cells expressed Rta, ORF K8, vIL-6, vMIP I, vBcl-2, PAN RNA, and sVCA [2].
  • We report a method of coupled CE-LIF detection with flow cytometry for high-throughput determination and quantitation of fluorophores in single intact K562/S (KS) cells [22].
  • A rifamycin-specific KS primer set was designed, and that primer set increased the number of rifamycin-positive strains detected by PCR screening relative to the number detectable using a conserved KS-specific set [3].
  • Sequence analysis indicated that pks4 encoded a 2009-amino acid polypeptide consisting of four functional domains: beta-ketoacyl synthase (KS), acyltransferase (AT), acyl carrier (ACP), and thioesterase (TE) [23].
  • A cDNA fragment of the cps gene from the fungus G. fujikuroi was amplified by RT-PCR using oligonucleotides based on amino-acid sequences which were conserved between the plant CPSs and the bifunctional CPS/KS of the fungus Phaeosphaeria sp. L487 [24].


  1. Cloning and expression of the multifunctional human fatty acid synthase and its subdomains in Escherichia coli. Jayakumar, A., Huang, W.Y., Raetz, B., Chirala, S.S., Wakil, S.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression. Sun, R., Lin, S.F., Staskus, K., Gradoville, L., Grogan, E., Haase, A., Miller, G. J. Virol. (1999) [Pubmed]
  3. Discovery of a new source of rifamycin antibiotics in marine sponge actinobacteria by phylogenetic prediction. Kim, T.K., Hewavitharana, A.K., Shaw, P.N., Fuerst, J.A. Appl. Environ. Microbiol. (2006) [Pubmed]
  4. Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: relation to ataxia. Sullivan, E.V., Deshmukh, A., Desmond, J.E., Lim, K.O., Pfefferbaum, A. Neuropsychology. (2000) [Pubmed]
  5. Evolutionary diversity of ketoacyl synthases in cellulolytic myxobacterium Sorangium. Li, Z.F., Zhao, J.Y., Xia, Z.J., Shi, J., Liu, H., Wu, Z.H., Hu, W., Liu, W.F., Li, Y.Z. Syst. Appl. Microbiol. (2007) [Pubmed]
  6. The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase. Tang, Y., Kim, C.Y., Mathews, I.I., Cane, D.E., Khosla, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Kuhajda, F.P., Pizer, E.S., Li, J.N., Mani, N.S., Frehywot, G.L., Townsend, C.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Human fatty acid synthase: properties and molecular cloning. Jayakumar, A., Tai, M.H., Huang, W.Y., al-Feel, W., Hsu, M., Abu-Elheiga, L., Chirala, S.S., Wakil, S.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Evolutionary implications of bacterial polyketide synthases. Jenke-Kodama, H., Sandmann, A., Müller, R., Dittmann, E. Mol. Biol. Evol. (2005) [Pubmed]
  10. Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells. Liu, B., Wang, Y., Fillgrove, K.L., Anderson, V.E. Cancer Chemother. Pharmacol. (2002) [Pubmed]
  11. Diterpene synthesis in Stevia rebaudiana: recruitment and up-regulation of key enzymes from the gibberellin biosynthetic pathway. Richman, A.S., Gijzen, M., Starratt, A.N., Yang, Z., Brandle, J.E. Plant J. (1999) [Pubmed]
  12. Origin of starter units for erythromycin biosynthesis. Weissman, K.J., Bycroft, M., Staunton, J., Leadlay, P.F. Biochemistry (1998) [Pubmed]
  13. Type I polyketide synthases may have evolved through horizontal gene transfer. Ginolhac, A., Jarrin, C., Robe, P., Perrière, G., Vogel, T.M., Simonet, P., Nalin, R. J. Mol. Evol. (2005) [Pubmed]
  14. Mechanism of the beta-ketoacyl synthase reaction catalyzed by the animal fatty acid synthase. Witkowski, A., Joshi, A.K., Smith, S. Biochemistry (2002) [Pubmed]
  15. Kaposi's sarcoma: clinico-pathological analysis of human immunodeficiency virus (HIV) and non-HIV associated cases. Hong, A., Lee, C.S. Pathol. Oncol. Res. (2002) [Pubmed]
  16. Application of an enzyme-linked immunosorbent-inhibition assay to quantitate the release of KS peptides into fluids of the rat subcutaneous air-pouch model and the effects of chondroprotective drugs on the release process. Kongtawelert, P., Francis, D.J., Brooks, P.M., Ghosh, P. Rheumatol. Int. (1989) [Pubmed]
  17. Functional analysis of the two interacting cyclase domains in ent-kaurene synthase from the fungus Phaeosphaeria sp. L487 and a comparison with cyclases from higher plants. Kawaide, H., Sassa, T., Kamiya, Y. J. Biol. Chem. (2000) [Pubmed]
  18. Conversion of a beta-ketoacyl synthase to a malonyl decarboxylase by replacement of the active-site cysteine with glutamine. Witkowski, A., Joshi, A.K., Lindqvist, Y., Smith, S. Biochemistry (1999) [Pubmed]
  19. Biochemical analysis of the substrate specificity of the beta-ketoacyl-acyl carrier protein synthase domain of module 2 of the erythromycin polyketide synthase. Wu, J., Kinoshita, K., Khosla, C., Cane, D.E. Biochemistry (2004) [Pubmed]
  20. An unusual beta-ketoacyl:acyl carrier protein synthase and acyltransferase motifs in TaK, a putative protein required for biosynthesis of the antibiotic TA in Myxococcus xanthus. Paitan, Y., Orr, E., Ron, E.Z., Rosenberg, E. FEMS Microbiol. Lett. (2001) [Pubmed]
  21. A spontaneous albino mutant of Ceratocystis resinifera results from a point mutation in the polyketide synthase gene, PKS1. Tanguay, P., Loppnau, P., Morin, C., Bernier, L., Breuil, C. Can. J. Microbiol. (2006) [Pubmed]
  22. CE-LIF coupled with flow cytometry for high-throughput quantitation of fluorophores in single intact cells. Xiao, H., Li, X., Zou, H., Yang, L., Wang, Y., Wang, H., Le, X.C. Electrophoresis (2006) [Pubmed]
  23. The polyketide synthase gene pks4 from Gibberella fujikuroi encodes a key enzyme in the biosynthesis of the red pigment bikaverin. Linnemannstöns, P., Schulte, J., del Mar Prado, M., Proctor, R.H., Avalos, J., Tudzynski, B. Fungal Genet. Biol. (2002) [Pubmed]
  24. Gibberellin biosynthesis in Gibberella fujikuroi: cloning and characterization of the copalyl diphosphate synthase gene. Tudzynski, B., Kawaide, H., Kamiya, Y. Curr. Genet. (1998) [Pubmed]
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