PMID:14693539

Citation	Jensen, SE, Paradkar, AS, Mosher, RH, Anders, C, Beatty, PH, Brumlik, MJ, Griffin, A and Barton, B (2004) Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. Antimicrob. Agents Chemother. 48:192-202
Abstract	An approximately 12.5-kbp region of DNA sequence from beyond the end of the previously described clavulanic acid gene cluster was analyzed and found to encode nine possible open reading frames (ORFs). Involvement of these ORFs in clavulanic acid biosynthesis was assessed by creating mutants with defects in each of the ORFs. orf12 and orf14 had been previously reported to be involved in clavulanic acid biosynthesis. Now five additional ORFs are shown to play a role, since their mutation results in a significant decrease or total absence of clavulanic acid production. Most of these newly described ORFs encode proteins with little similarity to others in the databases, and so their roles in clavulanic acid biosynthesis are unclear. Mutation of two of the ORFs, orf15 and orf16, results in the accumulation of a new metabolite, N-acetylglycylclavaminic acid, in place of clavulanic acid. orf18 and orf19 encode apparent penicillin binding proteins, and while mutations in these genes have minimal effects on clavulanic acid production, their normal roles as cell wall biosynthetic enzymes and as targets for beta-lactam antibiotics, together with their clustered location, suggest that they are part of the clavulanic acid gene cluster.
Links	PubMed PMC310172
Keywords	Anti-Bacterial Agents/biosynthesis; Chromatography, High Pressure Liquid; Clavulanic Acid/biosynthesis; DNA Mutational Analysis; DNA Transposable Elements; DNA, Fungal/biosynthesis; DNA, Fungal/genetics; Drug Resistance, Fungal; Mass Spectrometry; Multigene Family; Mutation/genetics; Plasmids/genetics; Streptomyces/genetics; Streptomyces/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STRCL:Q8KRB4		GO:0033050: clavulanic acid biosynthetic process	ECO:0000315:		P		Table 4 shows that when the orf15 gene is not present the cells can not produce clavulanic acid.	complete CACAO 4564
STRCL:Q8KRB4	involved_in	GO:0033050: clavulanic acid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
STRCL:Q83Z61		GO:0033050 : clavulanic acid biosynthetic process	ECO:0000315:		P		Table 4 shows that when the orf16 gene is not present the cells can not produce clavulanic acid.	complete CACAO 4565
STRCL:Q83Z61	involved_in	GO:0033050: clavulanic acid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
STRCL:Q83Z60		GO:0033050: clavulanic acid biosynthetic process	ECO:0000315:		P		Table 4 shows that when the orf17 gene is not present the cells can not produce clavulanic acid.	complete CACAO 4566
STRCL:Q83Z60	involved_in	GO:0033050: clavulanic acid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
STRCL:Q8KRB5		GO:0033050: clavulanic acid biosynthetic process	ECO:0000315:		P		Table 4 shows that when the orf14 gene is not present the cells can not produce clavulanic acid	complete CACAO 4567
STRCL:Q8KRB5	involved_in	GO:0033050: clavulanic acid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
STRCL:Q83Z62		GO:0033050: clavulanic acid biosynthetic process	ECO:0000315:		P		Table 4 shows that when the orf12 gene is not present the cells can not produce clavulanic acid.	complete CACAO 4568
STRCL:Q83Z62	involved_in	GO:0033050: clavulanic acid biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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