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Corynebacterium glutamicum의 탄소대사 및 총체적 탄소대사 조절

Carbon Metabolism and Its Global Regulation in Corynebacterium glutamicum.

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한국미생물·생명공학회 (The Korean Society For Microbiology And Biotechnology)|2010.12|한국미생물·생명공학회지 (Microbiology and Biotechnology Letters)|제38권 제4호|pp. 349-361

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참고문헌

키워드

Corynebacterium glutamicumcarbon metabolismglobal carbon regulationcarbon catabolite repressiongene regulation
주제분류생물학

초록

본 총설에서는 아미노산의 공업적 생산균인 Corynebacterium glutamicum의 탄소 대사 및 이와 관련된 총체적 조절 메커니즘에 대한 최근의 연구를 정리하였다. C. glutamicum의산업적 발효을 위한 기질로서 사용되는 당밀은 주로 sucrose,glucose, fructose로 이루어져 있으며, 이들 당은 phosphotransferase system을 통해서 수송된다. C. glutamicum의 탄소 대사 특징은 glucose가 다른 당이나 유기산 등과 함께 존재할 때, glucose와 이러한 탄소원 들을 동시에 대사한다. 그러나 glucose/glutamate 혹은 glucose/ethanol 등의 혼합물에서는 탄소원의 순차적 이용으로 인해 나타나는 diauxic growth 현상을 나타내며, 이러한 carbon catabolite repression(CCR)현상은 E. coli나 B. subtilis 등에서 알려진 것과는 다른 독특한 분자적 메커니즘과 조절 circuits을 가지고 있음이 밝혀지고 있다. C. glutamicum의 CRP homologue인 GlxR은acetate 대사를 포함하여 glycolysis, gluconeogenesis 및TCA cycle 등을 포함하는 중심탄소대사 조절 뿐만 아니라,다양한 세포 기능의 조절에 관여하는 총체적 조절 단백질로서의 역할이 제시되고 있다. C. glutamicum의 adenylate cyclase(AC)는 막과 결합된 class IIIAC 로서, 막 단백질의특성상 아직 규명되어 있지 않은 세포 외부의 환경 변화에대응하여 세포 내의 cAMP합성 수준을 조절할 수 있는sensor로 추정할 수 있다. 특히 C. glutamicum의 경우 배지내 glucose 를 비롯한 탄소원과 cAMP 농도와의 관련성이E. coli에서 알려진 교과서적 지식과는 상반되게 변화하는 경향을 보이고 있어, cAMP signaling에 의한 세포 내 regulatory network 등은 향후 풀어야 할 의문으로 남아있다. 탄소대사 조절의 최상위에 존재하며 global 조절자인 GlxRcAMP 복합체 이외에도 차상위 전사조절 단백질로서 RamB,RamA, SugR 등이 존재하여 다양한 탄소대사를 조절한다. 최근 들어서는 새로운 탄소원으로서 대두되고 있는 biomass 관련 기질들을 이용할 수 있는 C. glutamucum 균주 구축을통하여 이용 기질의 범위를 확대시키고자 하는 연구 및 탄소 대사와 관련하여 L-lysine의 발효 수율 혹은 생산성을 향상시키고자 하는 다양한 분자적 균주 육종 연구 등이 수행되고 있다.

Abstract

In this review,the current knowledge of the carbon metabolism and global carbon regulation in Corynebacterium glutamicum are summarized. C. gluamicum has phosphotransferase system (PTS) for the utilization of sucrose, glucose, and fructose. C. glutamicum does not show any preference for glucose when various sugars or organic acids are present with glucose, and thus cometabolizes glucose with other sugars or organic acids. The molecular mechanism of global carbon regulation such as carbon catabolite repression (CCR) in C. glutamicum is quite different to that in Gram-negative or low-GC Gram-positive bacteria. GlxR (glyoxylate bypass regulator) in C. glutamicum is the cyclic AMP receptor protein (CRP) homologue of E. coli. GlxR has been reported to regulate genes involved in not only glyoxylate bypass, but also central carbon metabolism and CCR including glycolysis, gluconeogenesis, and tricarboxylic acid (TCA) cycle. Therefore, GlxR has been suggested as a global transcriptional regulator for the regulation of diverse physiological processes as well as carbon metabolism. Adenylate cyclase of C. glutamicum is a membrane protein belonging to class III adenylate cyclases, thus it could possibly be a sensor for some external signal, thereby modulating cAMP level in response to environmental stimuli. In addition to GlxR, three additional transcriptional regulators like RamB, RamA, and SugR are also involved in regulating the expression of many genes of carbon metabolism. Finally, recent approaches for constructing new pathways for the utilization of new carbon sources, and strategies for enhancing amino acid production through genetic modification of carbon metabolism or regulatory network are described.

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