乙酰辅酶A羧化酶：脂肪酸代谢的关键酶及其基因克隆研究进展

Acetyl-coenzyme A Carboxylase:A Key Metabolic Enzyme of Fatty Acid and Progress of Its Gene Clone

乙酰辅酶A羧化酶(Acetyl-CoA carboxylase,ACC)在脂肪酸合成和分解代谢中发挥着重要作用.系统介绍了该酶的结构与分类、生物学作用与应用、抑制剂的类型与作用机理以及基因克隆4个方面的进展.ACC在大多数原核生物中为多亚基型酶,而在大多数真核生物中为多功能型单亚基酶,在天蓝色链霉菌和古菌勤奋金属球菌中为另外两种特殊类型;但都具备3个关键的功能域,即生物素羧化酶(BC)、生物素羧基载体蛋白(BCCP)和羧基转移酶(CT).CT功能域作为潜在的靶标广泛应用于植物除草剂的筛选和哺乳动物肥胖、糖尿病等代谢疾病的药物设计中.ACC基因也成为转基因油料作物和生物柴油研究中重要的靶标基因.研究表明,植物质体中的β-CT亚基是多亚基型ACC的限制因子,而BCCP是脂肪酸合成的负调控因子.油脂的合成代谢十分复杂,且存在反馈抑制机制,因此克隆和表达ACC基因可以提高宿主中ACC的活性,但不一定能显著促进脂肪酸的积累.

Acetyl-coenzyme A carboxylases（ACCs） have crucial roles in fatty acid metabolism in most living organisms.In this article,structure,types,functions and inhibitors of ACC,as well as research status of ACC gene clone are systematically discussed.ACC is a multi-subunit enzyme in most prokaryotes,whereas it is a large,multi-domain enzyme in most eukaryotes.In addition,there are two special types found from Streptomyces coelicolor and Metallosphaera sedula.All of these types contain three key domains： Biotin carboxylase（BC）,biotin carboxyl carrier protein（BCCP） and carboxyltransferase（CT）.CT domain,as a candidate target,has been widely used for screening of plant herbicides and drug development against obesity,diabetes and other symptoms of the metabolic syndrome.The gene encoded ACC is also becoming an important target gene applied in the fields of transgenic oil plants and biodiesel.Previous studies showed that β-CT in plant plasmid was the limit factor of heteromeric ACC,and BCCP was a negative regulator of fatty acid synthesis.Lipid synthesis metabolism is a very complex network,especially feedback inhibition mechanism exists in it.As a result,cloning and expression of ACC gene may increase the activity of ACC in the host,but not necessarily could obviously promote the accumulation of fatty acid.Fig 2,Ref 52