title: Roles of type II thioesterases and their application for secondary metabolite yield improvement.
abstract: A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from simple substrates, such as carboxylic acids and amino acids. Modular PKSs and NRPSs, often referred to as megasynthases, have brought about a special interest due to the colinearity between enzymatic domains in the proteins working as an "assembly line" and the chain elongation and modification steps. Extensive efforts toward modified compound biosynthesis by changing organization of PKS and NRPS domains in a combinatorial manner laid good grounds for rational design of new structures and their controllable biosynthesis as proposed by the synthetic biology approach. Despite undeniable progress made in this field, the yield of such "unnatural" natural products is often not satisfactory. Here, we focus on type II thioesterases (TEIIs)--discrete hydrolytic enzymes often encoded within PKS and NRPS gene clusters which can be used to enhance product yield. We review diverse roles of TEIIs (removal of aberrant residues blocking the megasynthase, participation in substrate selection, intermediate, and product release) and discuss their application in new biosynthetic systems utilizing PKS and NRPS parts.
authors: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114, Wroclaw, Poland, szulc@iitd.pan.wroc.pl.
authors: Magdalena
authors: M
authors: Kotowska
authors: Krzysztof
authors: K
authors: Pawlik
mesh_terms: D001709:Biotechnology; D064429:Fatty Acid Synthases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010453:Peptide Synthases / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism*; D013379:Substrate Specificity; D013869:Thiolester Hydrolases / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D048630:Polyketide Synthases; D064429:Fatty Acid Synthases; D013869:Thiolester Hydrolases; C022738:thioesterase II; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase