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Microbial MetabolismProduction and Regulation of Primary and Secondary MetabolitesChing-Tsan Huang (黃慶璨)Office: Agronomy Hall, Room 111Tel: (02) 33664454E-mail: cthuang@ntu.edu.tw

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Products of Microbiology

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Primary Metabolites

Small molecules of living cellsIntermediates or end products of the pathwayRelated to synthesis of microbial cells in the growth phaseInclude alcohols, amino acids, nucleotides, organic acids, polyols, vitamins, and enzymes

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Secondary Metabolites

Accumulate following active growthHave no direct relationship to synthesis of cell material and natural growthInclude antibiotics and toxins

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Primary metabolic pathwayfor the synthesis of aromatic amino acids

The secondary metaboliteantibiotics containing aromatic rings.

Relation between 1o and 2o metabolic pathway

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Regulation Mechanisms

Central Dogma

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Modification of Gene Expressionallows for overproduction of a product, production of more than one product by the same organism, or synthesis of modified products

Pathway architectureanalysis, design, and modification of biochemical pathways to increase process efficiency

Metabolic pathway engineeringintentional alteration of metabolic pathway by inactivation of specific genes

Metabolic control engineeringalteration of control mechanisms of specific genes

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Feedback inhibition of enzyme activity

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Specific Feedback Inhibition

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Enzyme Inhibition by Allosteric Effector

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Inactive

Active

Negative Control of TranscriptionRepression

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Negative Control of Transcription

Inactive

Active

Induction

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Positive Control of Enzyme Induction

Inactive

Active

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Positive Control of Transcription

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Catabolite RepressionOccurs when operon is under control of catabolite other than initial substrateAllows preferential use of one carbon source over another

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Transcription of trp operon by attenuation

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Transcription of trp operon by attenuation

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Two-Component System

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Production of Vinegar

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Citric Acid Fermentation

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Antibiotics

Requires precise control of nutrients Final product can be modified to yield a variety of semisynthetic penicillins

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Biosynthetic Pathway of Penicillin

ACV synthetase

IPN synthetase

Acyltransferase

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Industrial Production of Penicillins