Recent advances in the biochemistry of spinosyns.
Spinosyn and its analogs, produced by Saccharopolyspora spinosa, are the active ingredients in a family of insect control agents. They are macrolides with a 21-carbon, 12-membered tetracyclic lactones that are attached to two deoxysugars, tri-O-methylrhamnose and forosamine. Labeling studies, analysis of the biosynthetically blocked mutants, and the genetic identification of the spinosyn gene cluster have provided detailed information concerning the mechanism of spinosyn biosynthesis and have enabled combinatorial biosynthesis of a large group of new spinosyns. The following developments have recently impacted the field of spinosyn biology: (1) A second-generation spinosyn called spinetoram (XDE-175) was launched in late 2007; it is a semisynthesized spinosyn derivative produced through the modification of 3'-O-methyl group of rhamnose and the double bond between C5 and C6 of spinosyn J and L. This molecule was shown to have improved insecticidal activity, enhanced duration of control, and an expanded pest spectrum. (2) A new class of spinosyns, the butenyl-spinosyns, was discovered from Saccharopolyspora pogona. The butenyl-spinosyns are similar to spinosyns, but differ in the length of the side chain at C-21. In addition to structural similarities with the spinosyns, the butenyl-spinosyns exhibit a high level of similarity in insecticidal activity to spinetoram. (3) Spinosyn analogs, 21-cyclobutyl-spinosyn A and 21-cyclobutyl-spinosyn D were generated by metabolic engineering of the spinosyn biosynthetic gene cluster. They showed better insecticidal activities against cotton aphid and tobacco budworm than that of spinosyn A and D. Future progress toward the development of more potent spinosad analogs, as well as enhancements in production yields will likely result from these recent advances in the genetics and biochemistry of spinosyns.
Huang
Ke-xue
KX
Key Laboratory of Microbial Molecular Biology of Hunan Province, College of Life Science, Hunan Normal University, Changsha, 410081, China. huangkx@hunnu.edu.cn
Xia
Liqiu
L
Zhang
Youming
Y
Ding
Xuezhi
X
Zahn
James A
JA
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001671:Biochemistry; D053898:Biosynthetic Pathways; D005818:Genetic Engineering; D007313:Insecta / Q000187:drug effects; D007306:Insecticides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016930:Saccharopolyspora / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D007306:Insecticides; D018942:Macrolides; C548262:spinetoram