title: Structural Diversification of Lyngbyatoxin A by Host-Dependent Heterologous Expression of the tleABC Biosynthetic Gene Cluster.
abstract: Natural products have enormous structural diversity, yet little is known about how such diversity is achieved in nature. Here we report the structural diversification of a cyanotoxin-lyngbyatoxin A-and its biosynthetic intermediates by heterologous expression of the Streptomyces-derived tleABC biosynthetic gene cluster in three different Streptomyces hosts: S. lividans, S. albus, and S. avermitilis. Notably, the isolated lyngbyatoxin derivatives, including four new natural products, were biosynthesized by crosstalk between the heterologous tleABC gene cluster and the endogenous host enzymes. The simple strategy described here has expanded the structural diversity of lyngbyatoxin A and its biosynthetic intermediates, and provides opportunities for investigation of the currently underestimated hidden biosynthetic crosstalk.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Lihan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Hoshino
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Awakawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.|Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Wakimoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D001426:Bacterial Proteins; D044822:Biodiversity; D001688:Biological Products / Q000737:chemistry; D005798:Genes, Bacterial; D008235:Lyngbya Toxins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D015394:Molecular Structure; D005810:Multigene Family; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products; D008235:Lyngbya Toxins; C019457:lyngbyatoxin A
keywords: alkaloids; biosynthesis; heterologous expression; natural products; pathway crosstalk