title: Lovastatin production: From molecular basis to industrial process optimization.
abstract: Lovastatin, composed of secondary metabolites produced by filamentous fungi, is the most frequently used drug for hypercholesterolemia treatment due to the fact that lovastatin is a competitive inhibitor of HMG-CoA reductase. Moreover, recent studies have shown several important applications for lovastatin including antimicrobial agents and treatments for cancers and bone diseases. Studies regarding the lovastatin biosynthetic pathway have also demonstrated that lovastatin is synthesized from two-chain reactions using acetate and malonyl-CoA as a substrate. It is also known that there are two key enzymes involved in the biosynthetic pathway called polyketide synthases (PKS). Those are characterized as multifunctional enzymes and are encoded by specific genes organized in clusters on the fungal genome. Since it is a secondary metabolite, cultivation process optimization for lovastatin biosynthesis has included nitrogen limitation and non-fermentable carbon sources such as lactose and glycerol. Additionally, the influences of temperature, pH, agitation/aeration, and particle and inoculum size on lovastatin production have been also described. Although many reviews have been published covering different aspects of lovastatin production, this review brings, for the first time, complete information about the genetic basis for lovastatin production, detection and quantification, strain screening and cultivation process optimization. Moreover, this review covers all the information available from patent databases covering each protected aspect during lovastatin bio-production.
authors: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasilia, Brasília, DF 70790-160, Brazil.
authors: Kelly C L
authors: KC
authors: Mulder
authors: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasilia, Brasília, DF 70790-160, Brazil.
authors: Flávia
authors: F
authors: Mulinari
authors: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasilia, Brasília, DF 70790-160, Brazil.
authors: Octávio L
authors: OL
authors: Franco
authors: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasilia, Brasília, DF 70790-160, Brazil; Grupo de Engenharia Metabólica Aplicada a Bioprocessos, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF CEP 70790-900, Brazil.
authors: Maria S F
authors: MS
authors: Soares
authors: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasilia, Brasília, DF 70790-160, Brazil.
authors: Beatriz S
authors: BS
authors: Magalhães
authors: Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasilia, Brasília, DF 70790-160, Brazil; Grupo de Engenharia Metabólica Aplicada a Bioprocessos, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF CEP 70790-900, Brazil. Electronic address: nadiasp@unb.com.br.
authors: Nádia S
authors: NS
authors: Parachin
mesh_terms: D001230:Aspergillus / Q000737:chemistry / Q000378:metabolism; D005285:Fermentation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D008148:Lovastatin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D060847:Metabolic Engineering
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin
keywords: Aspergillus terreus; HMG-CoA inhibitors; Hypercholesterolemia; Lovastatin; Secondary metabolites