Avermectin: biochemical and molecular basis of its biosynthesis and regulation

  title={Avermectin: biochemical and molecular basis of its biosynthesis and regulation},
  author={Y J Yoon and E.S. Kim and Yong-Soon Hwang and C.-Y. Choi},
  journal={Applied Microbiology and Biotechnology},
  • Y. Yoon, E.S. Kim, C. Choi
  • Published 1 February 2004
  • Chemistry, Biology
  • Applied Microbiology and Biotechnology
Abstract Avermectin and its analogues, produced by Streptomyces avermitilis, are major commercial antiparasitic agents in the field of animal health, agriculture, and human infections. They are 16-membered pentacyclic lactone compounds derived from polyketide and linked to a disaccharide of the methylated deoxysugar l-oleandrose. Labeling studies, analyses of the biosynthetically blocked mutants, and the identification of the avermectin gene cluster allows characterization of most of the… 
Recent advances in biochemistry and biotechnological synthesis of avermectins and their derivatives
This review has summarized and analyzed the update in advanced progress in biochemistry and biotechnological approaches used for the production of AVMs and their derivatives to facilitate further strain improvement and biosynthesis of novel derivatives bearing stable and improved biological activities.
Reverse biological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitilis
The results indicate that manipulating the key genes revealed by reverse engineering can effectively improve the yield of the target metabolites, providing a route to optimize production in these complex regulatory systems.
Overexpression of the ABC transporter AvtAB increases avermectin production in Streptomyces avermitilis
It is proposed that the AvtAB transporter exports avermectin, and thus reduces the feedback inhibition on avermECTin production inside the cell, and may be useful for enhancing the production of other antibiotics.
Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase
Two new avermECTin derivatives 25-methyl and 25-ethyl ivermectin were generated by the domain swap of avermctin PKS and implied the potential use as insecticide in agriculture.
SAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development
It is demonstrated that a novel AraC-family transcriptional regulator in this species, SAV742, is a global regulator that negatively controls avermectin biosynthesis and cell growth, but positively controls morphological differentiation.
Enhanced production of avermectin by deletion of type III polyketide synthases biosynthetic cluster rpp in Streptomyces avermitilis
Transcriptional analysis suggested that the deletion of rpp gene cluster stimulated transcription of aveR, leading to increased transcription of biosynthetic gene aveA1 and a consequent increase in avermectin production.
Natural Biocombinatorics in the Polyketide Synthase Genes of the Actinobacterium Streptomyces avermitilis
The results indicate that homologous recombination facilitated by the modularity of PKS architecture is the most important mechanism underlying polyketide diversity in bacteria.
Analysis of neutral lipid biosynthesis in Streptomyces avermitilis MA-4680 and characterization of an acyltransferase involved herein
The highly conserved HHAxxDG active site motif found in AtfA, which is present in SAV7256, as well as the similar hydrophobicity profiles of Atf a and SAV 7256 indicate a similar structure and function of both proteins.


Studies on the biosynthesis of avermectins.
Engineering the aveC gene to enhance the ratio of doramectin to its CHC-B2 analogue produced in Streptomyces avermitilis.
High-throughput screening of cultures grown on solid-phase fermentation plates and analysis using electrospray mass spectrometry was implemented to significantly increase screening capability, and an aveC gene with mutations that result in a 4-fold improvement in the ratio of doramectin to CHC-B2 was identified.
Deletion analysis of the avermectin biosynthetic genes of Streptomyces avermitilis by gene cluster displacement
Analysis of the avermectin phenotypes of the deletion-containing strains defined the extent and ends of the 95-kb avr gene cluster, identified a regulatory region, and mapped several avr functions.
Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites
  • S. Ōmura, H. Ikeda, M. Hattori
  • Biology, Engineering
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is
Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis
The complete nucleotide sequence of the linear chromosome of Streptomyces avermitilis is determined and it is revealed that an internal 6.5-Mb region in the S. avermitILis genome was highly conserved with respect to gene order and content, and contained all known essential genes but showed perfectly asymmetric structure at the oriC center.
Identification of a cyclohexylcarbonyl CoA biosynthetic gene cluster and application in the production of doramectin
The CHC-CoA biosynthetic gene cluster represents an important genetic tool for precursor-directed biosynthesis of doramectin and has potential for directed biosynthesis in other important polyketide-producing organisms.
Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases
The analysis of the incorporation of 13C-labeled precursors into avermectins indicates that the avermectin aglycons are synthesized by head-to-tail condensation of various acyl groups, which is
Branched-chain fatty acid requirement for avermectin production by a mutant of Streptomyces avermitilis lacking branched-chain 2-oxo acid dehydrogenase activity.
It was concluded that acetate and propionate production by branched-chain 2-oxo acid degradation is not absolutely essential for avermectin production and novel isomeric avertmectins unseen in the (unsupplemented) wild-type strain are found.
Direct production of 5-oxo derivatives of avermectins by a recombinant strain of Streptomyces avermitilis.
5-Oximederivatives of milbemycins, which are structurally related to avermectins, have been also modified for similar purposes to attain enhanced potency.