【摘 要】
：
Fusidane-type antibiotics,represented by helvolic acid,fusidic acid and cephalosporin P1,are fungi-derived antimicrobials with little cross-resistance to co mmonly used antibiotics.Generation of new fusidane-type derivatives is therefore of great value,bu
【机 构】
：
College of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,Chi
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Fusidane-type antibiotics,represented by helvolic acid,fusidic acid and cephalosporin P1,are fungi-derived antimicrobials with little cross-resistance to co mmonly used antibiotics.Generation of new fusidane-type derivatives is therefore of great value,but this is hindered by available approaches.Here,we developed a stochastic combinational strategy by random asse.mbly of all the post-tailoring genes derived from helvolic acid,fusidic acid,and cephalosporin P1 biosynthetic pathways in a strain that produces their common intermediate.Among a total of 27 gene combinations,24 combinations produce expected prod-ucts and afford 58 fusidane-type analogues,of which 54 are new compounds.Moreover,random gene combination can induce unexpected activity of some post-tailoring enzymes,leading to a further increase in chemical diversity.These newly generated derivatives provide new insights into the structure-activity relationship of fusidane-type antibiotics.The stochastic combinational strategy established in this study proves to be a powerful approach for expanding structural diversity of natural products.
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