title: Effect of starter unit availability on the spectrum of manumycin-type metabolites produced by Streptomyces nodosus ssp. asukaensis.
abstract: OBJECTIVE
  Production of minor asukamycin congeners and its new derivatives by combination of targeted genetic manipulations with specific precursor feeding in the producer of asukamycin, Streptomyces nodosus ssp. asukaensis.
  
  
  RESULTS
  Structural variations of manumycins lie only in the diverse initiation of the 'upper' polyketide chain. Inactivation of the gene involved in the biosynthesis of cyclohexanecarboxylic acid (CHC) turned off the production of asukamycin in the mutant strain and allowed an increased production of other manumycins with the branched end of the upper chain. The ratio of produced metabolites was further affected by specific precursor feeding. Precursor-directed biosynthesis of a new asukamycin analogue (asukamycin I, 28%) with linear initiation of the upper chain was achieved by feeding norleucine to the mutant strain. Another asukamycin analogue with the unbranched upper chain (asukamycin H, 14%) was formed by the CHC-deficient strain expressing a heterologous gene putatively involved in the formation of the n-butyryl-CoA starter unit of manumycin A.
  
  
  CONCLUSIONS
  Combination of the described techniques proved to be an efficient tool for the biosynthesis of minor or novel manumycins.
  
  
  CONCLUSIONS
  Production of two novel asukamycin derivatives, asukamycins H and I, was achieved. Variations appeared in the upper polyketide chain, the major determinant of enzyme-inhibitory features of manumycins, affecting their cancerostatic or anti-inflammatory features.
authors.affiliation: Institute of Microbiology AS CR, Prague, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Pospíšil
authors.forename: K
authors.initials: K
authors.lastname: Petříčková
authors.forename: P
authors.initials: P
authors.lastname: Sedmera
authors.forename: P
authors.initials: P
authors.lastname: Halada
authors.forename: J
authors.initials: J
authors.lastname: Olšovská
authors.forename: M
authors.initials: M
authors.lastname: Petříček
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D003470:Culture Media; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism; D005818:Genetic Engineering; D016254:Mutagenesis, Insertional; D009154:Mutation; D011090:Polyenes / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D003470:Culture Media; D003509:Cyclohexanecarboxylic Acids; D011090:Polyenes; D053284:Polyunsaturated Alkamides; C024343:butyryl-coenzyme A; C013404:asukamycin; C044895:cyclohexanecarboxylic acid; C054474:manumycin