以中科院院士,、上海交通大學(xué)教育部微生物代謝重點(diǎn)實(shí)驗(yàn)室教授鄧子新領(lǐng)銜的研究團(tuán)隊(duì)與中科院微生物研究所合作，最近在多氧霉素（又名多抗霉素,，寶麗安等）生物合成機(jī)理研究領(lǐng)域獲得突破,，從多氧霉素生物合成全基因簇克隆并獲得39個(gè)候選基因入手，最終確定了20個(gè)必需基因,，并一舉成功實(shí)現(xiàn)了多氧霉素在異源宿主中的工程化生產(chǎn),，奠定了代謝工程技術(shù)產(chǎn)業(yè)化利用的基礎(chǔ)。
據(jù)介紹,，該團(tuán)隊(duì)還系統(tǒng)結(jié)合分子遺傳學(xué),、生物化學(xué)及化學(xué)等多個(gè)學(xué)科的研究，成功提出了多氧霉素生物合成的遺傳學(xué)和生物化學(xué)模型,，相關(guān)研究成果于不久前在美國(guó)生物化學(xué)與分子生物學(xué)會(huì)會(huì)刊《生物化學(xué)雜志》上在線發(fā)表,，并已申請(qǐng)國(guó)家發(fā)明專利。這是鄧子新團(tuán)隊(duì)繼殺念菌素,、南昌霉素及井岡霉素等多種抗生素代謝工程研究取得一系列成果以來(lái),，在多氧霉素生物合成機(jī)理研究方面取得的又一原創(chuàng)性、系統(tǒng)性研究成果,。
多氧霉素是世界上防治一些重要農(nóng)作物,、經(jīng)濟(jì)植物及果蔬真菌性病害的最佳生物農(nóng)藥之一，已顯示出高效無(wú)毒,、對(duì)環(huán)境友好且尚無(wú)耐藥性出現(xiàn)等優(yōu)良特性,。自多氧霉素成功創(chuàng)制以來(lái)，一直是我國(guó)及世界各國(guó)廣泛生產(chǎn)和使用的重要生物農(nóng)藥之一,。長(zhǎng)期以來(lái),，科學(xué)家們對(duì)該抗生素的生物合成具有濃厚興趣，但其生物合成機(jī)理卻一直懸而未決,。
博士生陳文青在這項(xiàng)持續(xù)4年的研究中,，充分顯示出系統(tǒng)性創(chuàng)新能力,。他最近還闡明了多氧霉素多個(gè)組分之間轉(zhuǎn)換的分子機(jī)制,，孕育著利用高新技術(shù)對(duì)多氧霉素工業(yè)菌株進(jìn)行活性組分優(yōu)化和產(chǎn)量提高的重大潛力，已經(jīng)引起有關(guān)生物農(nóng)藥生產(chǎn)企業(yè)的高度關(guān)注和重視,。該企業(yè)已經(jīng)開始了與鄧子新研究團(tuán)隊(duì)在多氧霉素代謝工程育種方面的合作,，以致力于提升我國(guó)多氧霉素產(chǎn)業(yè)化的技術(shù)水平和產(chǎn)品的競(jìng)爭(zhēng)力。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Biol. Chem, 10.1074/jbc.M807534200
Characterization of the polyoxin biosynthetic gene cluster from Streptomyces cacaoi and engineered production of polyoxin H
Wenqing Chen, Tingting Huang, Xinyi He, Qingqing Meng, Delin You, Linquan Bai, Jialiang Li, Mingxuan Wu, Rui li, Zhoujie Xie, Huchen Zhou, Xiufen Zhou, Huarong Tan, and Zixin Deng
Bio-X Life Science Research Center, Shanghai Jiaotong University, Shangahi
A gene cluster (pol) essential for the biosynthesis of polyoxin, a nucleoside antibiotic widely used for the control of phytopathogenic fungi, was cloned from Streptomyces cacaoi. A 46,066-bp region was sequenced and 20 out of 39 of the putative ORFs were defined as necessary for polyoxin biosynthesis as evidenced by its production in a heterologous host, Streptomyces lividans TK24. The role of PolO and PolA in polyoxin synthesis was demonstrated by in vivo experiments, and their functions were unambiguously characterized as O-carbamoyltransferase, and UMP- enolpyruvyl transferase, respectively by in vitro experiments, which enabled making of a modified compound differing slightly from that of early proposed. These studies should provide a solid foundation for the elucidation of the molecular mechanisms for polyoxin biosynthesis, and set the stage for combinatorial biosynthesis using genes encoding different pathways for nucleoside antibiotics.
