The role of ATP citrate lyase, malic enzyme and fatty acid synthase in the regulation of lipid accumulation in Cunninghamella sp. 2A1

Abstract

Identification of enzymes involved in the regulation of lipid biosynthesis in Cunninghamella sp. 2A1 was carried out by observing specific activity profile of seven lipogenic enzymes during lipid accumulation phase until cessation of lipogenesis occurred. Activities of all enzymes, 6-phosphogluconate dehydrogenase (6-PGDH), glucose-6-phosphogluconate dehydrogenase (G-6-PDH), NADP+:isocitrate dehidrogenase (NADP+:ICDH), malic enzyme (ME), ATP citrate lyase (ACL) and fatty acid synthase (FAS), increased when lipogenesis occurred after exhaustion of nitrogen in the culture. The enzymes remained active until the end of the experiment (79 h) except for ACL, ME and FAS which showed marked decreases (84, 72 and 59% respectively) in activity after 48 h. This decrease in activity coincided with the cessation of lipid accumulation at 48 h, although glucose was still present. This observation suggests that the three enzymes play a vital role in the down-regulation of lipid accumulation in Cunninghamella sp. 2A1. When 1 g/l ammonium tartrate was reintroduced into the culture at 60 h, the activity of ACL, ME and FAS was restored. This suggests that the decrease in ACL, ME and FAS activities was due to the depletion of nitrogen in the culture medium. The probable involvement of feedback inhibition in this observation is discussed.