Reviving the natural products legend path from natural screening to synthetic microbiology

来源 :第七届全国微生物资源学术暨国际微生物系统与分类学研讨会 | 被引量 : 0次 | 上传用户:dabing_12130
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  Synthetic biology combines biology and engineering technology to create new metabolic pathways,cells or organisms for useful purposes by designing and constructing new biological devices and systems.In this respect,synthetic microbiology seems leading the field,as many engineered microorganisms including Escherichia coli,Yeasts,or other microbes has now started to emerge for the successful production of fine chemicals and pharmaceuticals.In this talk,I will introduce some experimental examples of making new fine chemicals and natural products or their structural analogues in our laboratories by using the engineered microorganisms.An engineered E.coli strain has been constructed by combining Synechococcus elnogatus fatty acyl-ACP reductase and E.coli endogenous AdhP and can efficiently produce fatty alcohols-components of surfactants and cosmetic products-directly from glycerol.Furthermore,the high production of fatty acid short-chain esters,has been achieved also by using engineering an E.coli strain through combination of fatty acid and 2-keto acid pathways,which is now regarded as renewable and biodegradable biofuel molecules,some of which with the property of low freezing temperature.The mutant also produced esters with fruit perfume smell.When the same strategy was applied to S.cerevisia in a similar way for the reconstitution of the mevalonate pathway,terpenoid derived biofuel famesene was also successfully overproduced with a titer up to 1.1 g/L in shake flask.We also tried to engineer the iterative polyketide pathway from the secondary microbial metabolism for targeted pentadecane overproduction in E.coli,successfully and interestingly,a single form of alkane rather than a mixture of the reported fatty acids-derived pathway,was generated.Actinomycetes produce many natural products with bioactive diversities,the structural diversities of which,however,are not sufficient for the discovery of new pharmaceuticals and agrochemicals.By engineering Actinomycetes,producing strains of many clinically used antibiotics,natural products with greater chemo-diversity have been produced in our laboratories.Polyoxins and nikkomycins are potent antifungal peptidyl nucleoside antibiotics by inhibiting fungal cell wall biosynthesis.An engineered strain of Streptomyces aureochromogenes polyoxin producer constructed by combination of some biosynthetic genes of polyoxin and nikkomycin can produce polyoxin-nikkomycin hybrid compounds,some of which showed higher antifungal activity.These successful events suggested that synthetic microbiology would undoubtly show greater potential for structural modification and production of fine chemicals and natural products.
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