title: Enzymatic and chemo-enzymatic approaches towards natural and non-natural alkaloids: indoles, isoquinolines, and others.
abstract: The multi-step enzyme catalysed biosyntheses of monoterpenoid indole and isoquinoline alkaloids are described. Special emphasis is placed on those pathways leading to alkaloids of pharmacological and medicinal significance which have been fully elucidated at the enzyme level. The successful identification and cloning of cDNAs of single enzymes and their application provides great opportunities to develop novel strategies for both in vitro and in vivo alkaloid production in whole plants or tissue cultures, as well as in microbial systems such as Escherichia coli and yeast. Enzyme crystallisation, 3D analyses and site-directed mutation allowed rational engineering of enzyme substrate acceptance, which in turn can be used for reprogramming in vivo alkaloid biosynthesis and for the design of biomimetic alkaloid syntheses. These strategies broaden structural diversity and allow the creation of large libraries of unnatural alkaloid with expected optimised or novel biological activities. The chemo-enzymatic syntheses of the above-mentioned alkaloid groups and their precursors (in addition to selected examples of other alkaloid families) provides an overview of how enzyme reactions are integrated into the development of total chemical syntheses.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Zijingang Campus, 388 Yu Hang Tang Road, Hangzhou 310058, P. R. China. joesto2000@yahoo.com
authors.forename: Joachim
authors.initials: J
authors.lastname: Stöckigt
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Martin
authors.initials: M
authors.lastname: Ruppert
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D053898:Biosynthetic Pathways; D001709:Biotechnology / Q000379:methods* / Q000639:trends; D005658:Fungi / Q000201:enzymology / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods* / Q000639:trends; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010944:Plants / Q000201:enzymology / Q000235:genetics
chemical_list: D000470:Alkaloids; D007211:Indoles; D007546:Isoquinolines