Polyketide synthase Preu3-delta CMeT and application thereof in preparation of orsellinic acid

Abstract

The invention relates to a polyketide synthase Preu3-delta CMeT and application thereof in preparation of orsellinic acid, and belongs to the technical field of molecular biology and biochemistry. The amino acid sequence of the polyketide synthase Preu3-delta CMeT is as shown in SEQ ID NO.1, and the polyketide synthase Preu3-delta CMeT is constructed by taking polyketide synthase Preu3 derived from phorbia fungi as a material and knocking out a CMeT structural domain of the polyketide synthase Preu3-delta CMeT on the basis of a combined biosynthesis technology; the polyketide synthase Preu3-delta CMeT is transferred into saccharomyces cerevisiae to successfully obtain a mutant strain capable of efficiently producing the orsellinic acid; and the prepared orsellinic acid is taken as an object, the inhibitory activity of the orsellinic acid on clinical drug-resistant bacteria and crop pathogenic fungi is researched, and the orsellinic acid is found to have a very strong antagonistic effect on carbapenem-resistant pseudomonas aeruginosa, and the MIC is 12.5 [mu]g / mL. The polyketide synthase Preu3-delta CMeT greatly enriches the production sources of the orsellinic acid, and has important scientific value and application prospect for expanding the derivatization approach of the orsellinic acid and researching and developing a novel antibacterial agent.

Description

technical field [0001] The invention belongs to the technical field of molecular biology and biochemistry, and specifically relates to a novel "non-natural" polyketide synthase Preu3-ΔCMeT and its application in preparing orsinic acid. Background technique [0002] Fungal polyketides ( p oly k etide s , PKs) is a large class of important natural product groups with diverse chemical structures and biological activities, and is a high-quality resource library for the discovery of new drug lead compounds. Representative fungal PKs include lovastatin for lowering cholesterol, griseofulvin for fungi, rifamycin for bacteria, mycophenolic acid for immunosuppression, Actin and angiogenesis inhibitor cytochalasin E (cytochalasin E), etc. The key enzyme of PKs biosynthesis - fungal polyketide synthase ( p oly k etide s ynthase, PKS) is an iterative (iterative) type I PKS, and its domain usually includes: the initiation unit ACP transacylase ( s tarter unit A CP t ransacylase...

AI Technical Summary

Problems solved by technology

But at present, commercially available orsic acid (CAS: 480-64-8) is produced by chemical synthesis, and the price is about 1,000 yuan / 100mg. The output is low and the price is high, so its application in food, medicine and other fields is restricted. limit

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