title: Mutasynthesis of pyrrole spiroketal compound using calcimycin 3-hydroxy anthranilic acid biosynthetic mutant.
abstract: The five-membered aromatic nitrogen heterocyclic pyrrole ring is a building block for a wide variety of natural products. Aiming at generating new pyrrole-containing derivatives as well as to identify new candidates that may be of value in designing new anticancer, antiviral, and/or antimicrobial agents, we employed a strategy on pyrrole-containing compound mutasynthesis using the pyrrole-containing calcimycin biosynthetic gene cluster. We blocked the biosynthesis of the calcimycin precursor, 3-hydroxy anthranilic acid, by deletion of calB1-3 and found that two intermediates containing the pyrrole and the spiroketal moiety were accumulated in the culture. We then fed the mutant using the structurally similar compound of 3-hydroxy anthranilic acid. At least four additional new pyrrole spiroketal derivatives were obtained. The structures of the intermediates and the new pyrrole spiroketal derivatives were identified using LC-MS and NMR. One of them shows enhanced antibacterial activity. Our work shows a new way of pyrrole derivative biosynthetic mutasynthesis.
authors.affiliation: State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University, Yangling, Shannxi, 712100, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Gou
authors.forename: Qiulin
authors.initials: Q
authors.lastname: Wu
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Lin
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Li
authors.forename: Jingdan
authors.initials: J
authors.lastname: Liang
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhou
authors.forename: Derong
authors.initials: D
authors.lastname: An
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D000001:Calcimycin / Q000096:biosynthesis* / Q000737:chemistry; D005663:Furans / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D015394:Molecular Structure; D009154:Mutation; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005663:Furans; D011758:Pyrroles; D013141:Spiro Compounds; D062367:ortho-Aminobenzoates; C520774:spiroketal; C031385:anthranilic acid; D000001:Calcimycin