[Exploiting bioactive Enediynes from marine microbe based on activity and gene screening].
OBJECTIVE
A high quality library of marine microbes and their associated natural products is critical for successful drug discovery. In this research a method to assess the quality of our marine microbial natural product library through screening for novel enediyne-like compounds from this library was set up.


METHODS
A high throughput screening assay based on the unique DNA-damage activity of enediyne-like compounds has been constructed and our marine microbial natural product library was screened. Because the polyketide synthase responsible for the biosynthesis of enediyne core is a conserved iterative type I polyketide synthase, a sequence-based screening method was built to get the strains that harbored enediyne biosynthesis gene clusters.


RESULTS
Through activity-based screening, a positive hit from our marine natural product library was acquired. 16S rRNA analysis has revealed that this strain-LS481 was 99% similar to Micromonospora chersina DSM 44151T that could produce enediyne compound-Dynemicins. The crude extract of LS481 showed similar characteristics with Dynemicin A. In addition, two strains, MS098 and LS2004, were acquired through sequence-based screening. The 16S rRNA of MS098 was 100% the same as Streptomyces griseus NBRC 13350, and LS2004 was most close to Streptomyces vinaceus NBRC 13425? and Streptomyces cirratus NRRL B-3250T.


CONCLUSIONS
We can successfully isolate enediyne compounds through the activity-based screening and assess the potential of producing enediyne compounds through sequence-based screening.
Pei
Gang
G
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Dai
Huanqin
H
Ren
Biao
B
Liu
Xiangyang
X
Zhang
Lixin
L
D053281:Enediynes / Q000494:pharmacology*; D005798:Genes, Bacterial / Q000187:drug effects; D008386:Marine Biology; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000187:drug effects* / Q000235:genetics; D017422:Sequence Analysis, DNA
D053281:Enediynes