A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that catalyzes the first specific step in the biosynthesis of ergot alkaloids, was cloned from a strain of Claviceps purpurea that produces alkaloids in axenic culture. The derived gene product (CPD1) shows only 70% similarity to the corresponding gene previously isolated from Claviceps strain ATCC 26245, which is likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most probably represents the first C. purpurea gene coding for an enzymatic step of the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene named cpps1, which codes for a 356-kDa polypeptide showing significant similarity to fungal modular peptide synthetases. The protein contains three amino acid-activating modules, and in the second module a sequence is found which matches that of an internal peptide (17 amino acids in length) obtained from a tryptic digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome walking revealed the presence of additional genes upstream of cpd1 which are probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase), and a second putative oxidoreductase gene, cpox2, is closely linked to it in inverse orientation. RT-PCR experiments confirm that all four genes are expressed under conditions of peptide alkaloid biosynthesis. These results strongly suggest that at least some genes of ergot alkaloid biosynthesis in C. purpurea are clustered, opening the way for a detailed molecular genetic analysis of the pathway.
Background: The suppressor of cytokine signaling (SOCS)-3 is a negative feedback regulator of cytokine signaling and also influences leptin signaling. We investigated association of variations in the coding sequence and promoter region of SOCS3 with extreme obesity in German children and adolescents.
SummaryBackground: Several lines of evidence indicate an involvement of procolipase (CLPS) or its derivative enterostatin in dietary fat absorption, regulation of fat intake, and body weight in rodents. We explored the relationship between genetic variation in CLPS, early-onset obesity and fat intake in humans. Methods: We screened the CLPS in 93 extremely obese children and adolescents and 96 underweight young adults for sequence variations and genotyped single nucleotide polymorphisms (SNPs) in extremely obese children and adolescents, healthy normal-and underweight young adults and obesity trios. Case-control and family-based association analyses were performed. Results: Five sequence variations were identified: two non-synonymous SNPs: rs2766597 (Leu8Pro), rs41270082 (Arg109Cys); one SNP in the 5′UTR: rs3748050; one intronic SNP: rs3748051; and one infrequent novel non-synonymous variant: Arg55His. For rs2766597, rs3748050, and rs3748051 we obtained no evidence for an association with obesity in the case-control comparison. For rs41270082 there was a trend for association which could not be substantiated in the family-based association analysis. Additionally, we found no association in subgroup analyses pertaining to the extremely obese children and adolescents in the lowest and highest quartile of the percentage of energy consumed as fat. Conclusions: We found no evidence for an association of CLPS SNPs rs2766597, rs41270082, rs3748050, and rs3748051 with obesity or percentage of dietary fat intake.
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