%0 Journal Article %A Zhang, Yirong %A Bai, Linquan %A Deng, Zixin %T Functional characterization of the first two actinomycete 4-amino-4-deoxychorismate lyase genes %D 2009 %J Microbiology, %V 155 %N 7 %P 2450-2459 %@ 1465-2080 %R https://doi.org/10.1099/mic.0.026336-0 %K Apr, apramycin %K PLP, pyridoxal 5′-phosphate %K LDH, lactate dehydrogenase %K PABA, p-aminobenzoic acid %K aac(3)IV, apramycin-resistance gene %K ADC, 4-amino-4-deoxychorismate %K PermE*, up-mutated promoter of erythromycin-resistance gene %K PKS, polyketide synthase %I Microbiology Society, %X In some antibiotic producers, p-aminobenzoic acid (PABA) or its immediate precursor, 4-amino-4-deoxychorismate (ADC), is involved in primary metabolism and antibiotic biosynthesis. In Streptomyces sp. FR-008, a gene pabC-1 putatively encoding a fold-type IV pyridoxal 5′-phosphate (PLP)-dependent enzyme was found within the antibiotic FR-008/candicidin biosynthetic gene cluster, whose inactivation significantly reduced the productivity of antibiotic FR-008 to about 20 % of the wild-type level. Its specific role in PABA formation was further demonstrated by the successful complementation of an Escherichia coli pabC mutant. Moreover, a free-standing gene pabC-2, probably encoding another fold-type IV PLP-dependent enzyme, was cloned from the same strain. Inactivation of pabC-2 reduced antibiotic FR-008 yield to about 57 % of the wild-type level in the mutant, and the complementation of the E. coli pabC mutant established its involvement in PABA biosynthesis. Furthermore, a pabC-1/pabC-2 double mutant only retained about 4 % of the wild-type antibiotic FR-008 productivity, clearly indicating that pabC-2 also contributed to biosynthesis of this antibiotic. Surprisingly, apparently retarded growth of the double mutant was observed on minimal medium, which suggested that both pabC-1 and pabC-2 are involved in PABA biosynthesis for primary metabolism. Finally, both PabC-1 and PabC-2 were shown to be functional ADC lyases by in vitro enzymic lysis with the release of pyruvate. pabC-1 and pabC-2 appear to represent the first two functional ADC lyase genes identified in actinomycetes. The involvement of these two ADC lyase genes in both cell growth and antibiotic FR-008 biosynthesis sets an example for the interplay between primary and secondary metabolisms in bacteria. %U https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.026336-0