The Gene Mining Of Angucyclines And Related Secondary Metabolites

Natural products are an important source of clinical and pharmaceutical compounds and they also contribute with compounds showing agricultural and veterinary applications.A large proportion of natural products are synthesized by microorganisms which constitute a prolific source of structurally diverse bioactive metabolites and have yielded some of the most important products of the pharmaceutical industry.Angucyclines are aromatic polyketides that feature a tetracyclic benz[a]anthracene with complex and diverse structures and amaing bioactivities(eg.antimicrobial,antitumor,antiviral and enzyme inhibition activities).Generally,traditional activity-based screening of microbial strains and valuable natural products has its inherent limitation because some natural products cannot be synthesized under the normal condition.With the increasing knowledge of biosynthesis gene cluster for synthesizing natural products,functional gene-based analysis provides a useful approach for predicting natural products.The aim of this research is to discover angucyclines from actinomycetes through genome mining way.This paper can be divided into two charpters,one is genome mining angucyclines from R1701-1 and WY1801;and the other is to set up a homology-dependent PCR approach to abtain potential angucyclines producers.34 Streptomyces strains from 150 different Streptomyces strains were found to be with the potential aromatic polyketides producer based on the analysis of KSα(ketoacyl-synthase)gene in the PKS Ⅱ(type Ⅱ polyketides synthase)gene cluster.Among the 34 strains,angucycline cyclase gene was amplified in 6 strains(OC1610-4、R1706-1、HK70、WY1801、QF1802 and R1701-1),suggesting their potential in synthesizing angucyclines.This research gene-based PCR assay targeting type Ⅱ polyketides synthase and angucyclines cyclase,and combined chemical analysis.The strain N1510-2、FQ3、R1702-1、R1701-1 and WY1801 were choosed to frement and separate products.The 23 compounds were isolated from the five Streptomyces strains;including six angucyclines,six aromatic polyketides(Julichromes),three strepantibins,three actinomycins,three germicidins,one acid compound and plasticizer;among the isolated compounds,strepantibin D,strepantibin E,julichrome Q3.13 and julichrome Q3.14 were new compound.