Tissue culture-generated shoot-based clonal lines of oregano that have a short and long life span during in vitro culture were investigated to determine the role of proline-linked pentose phosphate pathway in modulating phenolic response following ultraviolet (UV) exposure. This novel reductant cycling pathway for energy and oxidative pentose phosphate pathway (PPP) is more efficient in long life span O-17 clonal line in response to UV and this supported antioxidant response. UV treatment stimulated rosmarinic acid and associated antioxidant enzyme response in O-17 clonal line compared with short life span O-3 clonal line. Additionally, O-17 clonal line had higher glucose-6-phosphate dehydrogenase and guaicol peroxidase activity in response to UV exposure compared with O-3 clonal line, indicating stimulation of anabolic pathway supporting PPP during UV treatment. The stimulation of proline dehydrogenase (PDH) activity in O-17 clonal line in response to UV indicated a switch to PDH-linked energy pathway via proline oxidation.